frameshift mutation

Summary

Summary: A type of mutation in which a number of NUCLEOTIDES not divisible by three is deleted from or inserted into a protein coding sequence, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.

Top Publications

  1. ncbi A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
    Y Ogura
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 411:603-6. 2001
  2. pmc Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia
    Hanna T Gazda
    Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, 3 BlackfanCircle, Boston, MA 02115, USA
    Hum Mutat 33:1037-44. 2012
  3. pmc A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming
    Padraic G Fallon
    Institute of Molecular Medicine, Trinity College Dublin, Ireland
    Nat Genet 41:602-8. 2009
  4. pmc A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations
    Louise M Downs
    Canine Genetics, Animal Health Trust, Newmarket, United Kingdom
    PLoS ONE 6:e21452. 2011
  5. pmc Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation
    Denice M Hodgson-Zingman
    Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, USA
    N Engl J Med 359:158-65. 2008
  6. pmc Improvement of reading frame maintenance is a common function for several tRNA modifications
    J Urbonavicius
    Department of Microbiology, Umea University, S 90 187 Umeå, Sweden
    EMBO J 20:4863-73. 2001
  7. 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
  8. ncbi Late-onset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71
    L M Downs
    The Kennel Club Genetics Centre, Animal Health Trust, Newmarket, UK
    Anim Genet 44:169-77. 2013
  9. pmc Escherichia coli DNA polymerase IV mutator activity: genetic requirements and mutational specificity
    J Wagner
    Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya Ku, Tokyo 158 8501, Japan
    J Bacteriol 182:4587-95. 2000
  10. ncbi A novel frameshift mutation in FRMD7 causing X-linked idiopathic congenital nystagmus
    Xiang He
    Department of Genetics, National Research Institute for Family Planning, Beijing, China
    Genet Test 12:607-13. 2008

Detail Information

Publications366 found, 100 shown here

  1. ncbi A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
    Y Ogura
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nature 411:603-6. 2001
    ..7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is ..
  2. pmc Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia
    Hanna T Gazda
    Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, 3 BlackfanCircle, Boston, MA 02115, USA
    Hum Mutat 33:1037-44. 2012
    ..We also found a deletion in RPL19 and missense mutations in RPL3 and RPL23A, which may be variants of unknown significance. Together with RPL5, RPL11, and RPS7, RPL26 is the fourth RP regulating p53 activity that is linked to DBA...
  3. pmc A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming
    Padraic G Fallon
    Institute of Molecular Medicine, Trinity College Dublin, Ireland
    Nat Genet 41:602-8. 2009
    ....
  4. pmc A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations
    Louise M Downs
    Canine Genetics, Animal Health Trust, Newmarket, United Kingdom
    PLoS ONE 6:e21452. 2011
    ..94×10(-10), p(genome) = 1.0×10(-5)), where a 644 kb region was homozygous within cases. A frameshift mutation was identified in a solute carrier anion exchanger gene (SLC4A3) located within this region...
  5. pmc Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation
    Denice M Hodgson-Zingman
    Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, USA
    N Engl J Med 359:158-65. 2008
    ..members, we mapped an atrial fibrillation locus to chromosome 1p36-p35 and identified a heterozygous frameshift mutation in the gene encoding atrial natriuretic peptide...
  6. pmc Improvement of reading frame maintenance is a common function for several tRNA modifications
    J Urbonavicius
    Department of Microbiology, Umea University, S 90 187 Umeå, Sweden
    EMBO J 20:4863-73. 2001
    ..We propose that the improvement of reading frame maintenance has been and is the major selective factor for the emergence of new modified nucleosides...
  7. 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
    ..We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change...
  8. ncbi Late-onset progressive retinal atrophy in the Gordon and Irish Setter breeds is associated with a frameshift mutation in C2orf71
    L M Downs
    The Kennel Club Genetics Centre, Animal Health Trust, Newmarket, UK
    Anim Genet 44:169-77. 2013
    ..22 × 10(-8) , Pgenome  = 2.00 × 10(-5) ), where a 3.2-Mb region was homozygous within cases. A frameshift mutation was identified in C2orf71, a gene located within this region...
  9. pmc Escherichia coli DNA polymerase IV mutator activity: genetic requirements and mutational specificity
    J Wagner
    Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya Ku, Tokyo 158 8501, Japan
    J Bacteriol 182:4587-95. 2000
    ..These results are discussed with respect to the recently described biochemical characteristics of DNA Pol IV...
  10. ncbi A novel frameshift mutation in FRMD7 causing X-linked idiopathic congenital nystagmus
    Xiang He
    Department of Genetics, National Research Institute for Family Planning, Beijing, China
    Genet Test 12:607-13. 2008
    ..In this study, we identified a novel frameshift mutation (c.1274-1275delTG) in the FRMD7 gene in six XLICN pedigrees...
  11. ncbi Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise
    Joshua T Mendell
    Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 539 Broadway Research Building, 733 N Broadway, Baltimore, Maryland 21205, USA
    Nat Genet 36:1073-8. 2004
    ....
  12. pmc Endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(A) tracts
    Ivica Tamas
    Department of Molecular Evolution, Evolutionary Biology Centre, Uppsala University, SE 752 36 Uppsala, Sweden
    Proc Natl Acad Sci U S A 105:14934-9. 2008
    ..These features of homopolymeric tracts could be exploited to manipulate gene expression in small synthetic genomes...
  13. pmc Slip into something more functional: selection maintains ancient frameshifts in homopolymeric sequences
    Jennifer J Wernegreen
    Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA, USA
    Mol Biol Evol 27:833-9. 2010
    ..Although the advantage of the frameshift itself is less clear, it may offer a mechanism to lower effective gene expression by reducing but not eliminating transcripts that encode full-length proteins...
  14. pmc A frameshift mutation within LAMC2 is responsible for Herlitz type junctional epidermolysis bullosa (HJEB) in black headed mutton sheep
    Stefanie Mömke
    Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany
    PLoS ONE 6:e18943. 2011
    ..A two base pair deletion within exon 18 of the LAMC2 gene (FM872310:c.2746delCA) causes a frameshift mutation resulting in a premature stop codon (p...
  15. pmc Functional characterization and targeted correction of ATM mutations identified in Japanese patients with ataxia-telangiectasia
    Kotoka Nakamura
    Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90095 1732, USA
    Hum Mutat 33:198-208. 2012
    ..The probands were compound heterozygotes in seven families, and one (JPAT2) was homozygous for a frameshift mutation. All mutations--four frameshift, two nonsense, four large genomic deletions, and six affecting splicing--..
  16. ncbi Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients
    F W Van Leeuwen
    Graduate School for Neurosciences Amsterdam, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The Netherlands
    Science 279:242-7. 1998
    ..This type of transcript mutation is likely an important factor in the widely occurring nonfamilial early- and late-onset forms of Alzheimer's disease...
  17. pmc Cone-rod dystrophy and a frameshift mutation in the PROM1 gene
    Eran Pras
    Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, 70300, Israel
    Mol Vis 15:1709-16. 2009
    ..To identify the genetic cause underlying autosomal recessive cone-rod dystrophy (CORD) and high myopia...
  18. pmc A "gain of function" mutation in a protein mediates production of novel modified nucleosides
    Peng Chen
    Department of Molecular Biology, Umea University, S 901 87 Umea, Sweden
    EMBO J 24:1842-51. 2005
    The mutation sufY204 mediates suppression of a +1 frameshift mutation in the histidine operon of Salmonella enterica serovar Typhimurium and synthesis of two novel modified nucleosides in tRNA...
  19. pmc The modified wobble nucleoside uridine-5-oxyacetic acid in tRNAPro(cmo5UGG) promotes reading of all four proline codons in vivo
    S Joakim Nasvall
    Department of Molecular Biology, Umea University, S 90 187 Umeå, Sweden
    RNA 10:1662-73. 2004
    ....
  20. ncbi Positional cloning of the Werner's syndrome gene
    C E Yu
    Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, WA 98108, USA
    Science 272:258-62. 1996
    ..The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients...
  21. ncbi A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration
    M A Maw
    Biochemistry Department, University of Otago, PO Box 56, Dunedin, New Zealand
    Hum Mol Genet 9:27-34. 2000
    ..These findings suggest that loss of prominin causes retinal degeneration, possibly because of impaired generation of the evaginations and/or impaired conversion of the evaginations to disks...
  22. ncbi Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability
    S Markowitz
    Department of Medicine, University Hospitals of Cleveland, OH, USA
    Science 268:1336-8. 1995
    ..RII mutation, by inducing the escape of cells from TGF-beta-mediated growth control, links DNA repair defects with a specific pathway of tumor progression...
  23. pmc Homopolymeric tracts represent a general regulatory mechanism in prokaryotes
    Renato H Orsi
    Department of Food Science, Cornell University, Ithaca, NY 14853, USA
    BMC Genomics 11:102. 2010
    ..g., phase variation...
  24. ncbi Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation
    E De Baere
    Department of Medical Genetics, Ghent University Hospital, B 9000 Ghent, Belgium
    Hum Mol Genet 10:1591-600. 2001
    ..Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect...
  25. ncbi Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration
    Qi Zhang
    A Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
    Hum Mol Genet 11:993-1003. 2002
    ..Microdeletions resulting in a premature stop or a frameshift mutation result in very different retinal phenotypes, which are allele-specific and consistent for each mutation...
  26. ncbi Mutations in PYCR1 cause cutis laxa with progeroid features
    Bruno Reversade
    Institute of Medical Biology, A STAR, Singapore, Singapore
    Nat Genet 41:1016-21. 2009
    ..Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues...
  27. pmc Variation in efficiency of DNA mismatch repair at different sites in the yeast genome
    Joshua D Hawk
    Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 102:8639-43. 2005
    ..We demonstrate experimentally that frameshift mutation rates in yeast microsatellites depend on the genomic context and that this variation primarily reflects the ..
  28. ncbi A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting
    Olivier Namy
    Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
    Nature 441:244-7. 2006
    ..Together, the structural changes provide a mechanical explanation of how the pseudoknot manipulates the ribosome into a different reading frame...
  29. pmc Perilipin deficiency and autosomal dominant partial lipodystrophy
    Sheetal Gandotra
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 364:740-8. 2011
    ..These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue...
  30. pmc The Escherichia coli K-12 "wild types" W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels
    K F Jensen
    Institute of Biological Chemistry, University of Copenhagen, Denmark
    J Bacteriol 175:3401-7. 1993
    ....
  31. pmc Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients
    Bernard C Broughton
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, United Kingdom
    Proc Natl Acad Sci U S A 99:815-20. 2002
    ..There is a wide variability in clinical features among patients, which is not obviously related to the site or type of mutation...
  32. pmc A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae
    S L Holbeck
    National Cancer Institute Frederick Cancer Research and Development Center, ABL Basic Research Program, Maryland 21702 1201, USA
    Genetics 147:1017-24. 1997
    ..Analysis of spontaneous reversion in haploid strains suggested that Rev3p had a greater role in making point mutations than in frameshift mutations...
  33. ncbi Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema
    Aileen Sandilands
    Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    Nat Genet 39:650-4. 2007
    ..i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles...
  34. ncbi Hypersensitivity of tumor cell lines with microsatellite instability to DNA double strand break producing chemotherapeutic agent bleomycin
    Hai Ri Li
    The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cancer Res 64:4760-7. 2004
    ..These results may be useful in designing therapies for MSI-positive cancer...
  35. ncbi A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease)
    Mohammad M Rahman
    Laboratory of Clinical Pathology, Department of Veterinary Medicine, Kagoshima University, 1 21 24 Kohrimoto, Kagoshima 890 0065, Japan
    Vet J 194:412-6. 2012
    ..These results strongly suggest that the deletion is pathogenic...
  36. ncbi Frameshift mutation in the Dok1 gene in chronic lymphocytic leukemia
    Sanghoon Lee
    International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon 69008, France
    Oncogene 23:2287-97. 2004
    ..This is the first example of a Dok1 mutation in B-CLL and the data suggest that Dok1 might play a role in leukemogenesis...
  37. ncbi Autosomal recessive retinitis pigmentosa is associated with mutations in RP1 in three consanguineous Pakistani families
    S Amer Riazuddin
    Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland
    Invest Ophthalmol Vis Sci 46:2264-70. 2005
    ..To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa in three consanguineous Pakistani families...
  38. ncbi Dose-dependent inhibition of proteasome activity by a mutant ubiquitin associated with neurodegenerative disease
    Paula van Tijn
    Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands
    J Cell Sci 120:1615-23. 2007
    ....
  39. pmc Stress-induced beta-lactam antibiotic resistance mutation and sequences of stationary-phase mutations in the Escherichia coli chromosome
    Joseph F Petrosino
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 3411, USA
    J Bacteriol 191:5881-9. 2009
    ..The important evolutionary implication is that not only loss-of-function mutations but also change-of-function mutations can be generated by this mechanism...
  40. pmc Genetic analysis of the E site during RF2 programmed frameshifting
    Christina L Sanders
    Department of Biology, Wake Forest University, Winston Salem, NC 27106, USA
    RNA 13:1483-91. 2007
    ..These findings indicate that pairing between the deacyl-tRNA and the E-site codon opposes frameshifting. We discuss the implications of these findings on frame maintenance and on the RF2 programmed frameshift mechanism...
  41. pmc Does tumorigenesis select for or against mutations of the DNA repair-associated genes BRCA2 and MRE11?: considerations from somatic mutations in microsatellite unstable (MSI) gastrointestinal cancers
    Michiel S Van Der Heijden
    From the department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
    BMC Genet 7:3. 2006
    ..Somatic mutations of BRCA2 are rare in typical sporadic cancers. In tumors having microsatellite instability (MSI), somatic truncating mutations in a poly [A] tract of BRCA2 are reported on occasion...
  42. ncbi Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa
    Li Jia Chen
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong
    Invest Ophthalmol Vis Sci 51:2236-42. 2010
    ..5_6delGT provided further genetic evidence that haploinsufficiency of RP1 is not responsible for RP. The authors propose four classes of truncation mutations in the RP1 gene with different effects on the etiology of RP...
  43. ncbi Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28
    Linda M Peters
    Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA
    Hum Mol Genet 11:2877-85. 2002
    ..Sequencing of six candidate genes in the 1.4 cM linked region identified a frameshift mutation (1609-1610insC) resulting in a premature translation stop codon in exon 14 of the gene TFCP2L3 (..
  44. pmc Growth rate-related regulation of the ilvGMEDA operon of Escherichia coli K-12 is a consequence of the polar frameshift mutation in the ilvG gene of this strain
    B S Parekh
    Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine 92697, USA
    J Bacteriol 179:2086-8. 1997
    ..Unlike other wild-type E. coli strains, E. coli K-12 contains a polar frameshift mutation in the ilvG gene (R. P. Lawther, D. H. Calhoun, C. W. Adams, C. A. Hauser, J. Gray, and G. W...
  45. pmc A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy
    Marian A J Weterman
    Department of Genome Analysis AMC, Amsterdam, The Netherlands
    Hum Mol Genet 21:358-70. 2012
    ..This frameshift mutation (p.Leu708Argfx28) is located in the C-terminal RING finger motif of the encoded protein...
  46. pmc A gripping tale of ribosomal frameshifting: extragenic suppressors of frameshift mutations spotlight P-site realignment
    John F Atkins
    Biosciences Institute, University College, Cork, Ireland
    Microbiol Mol Biol Rev 73:178-210. 2009
    ..Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook "yardstick" model in which the number of ..
  47. ncbi Two novel patients with Bohring-Opitz syndrome caused by de novo ASXL1 mutations
    Pamela Magini
    Dipartimento di Scienze Ginecologiche, Ostetriche e Pediatriche, Universita di Bologna, Policlinico Sant Orsola Malpighi, U O Genetica Medica, Bologna, Italy
    Am J Med Genet A 158:917-21. 2012
    ..2407_2411del5 [p.Q803TfsX17] and c.2893C>T [p.R965X]). These new data further support ASXL1 as cause of BOS and may contribute to a more precise definition of the phenotype caused by the disruption of this gene...
  48. ncbi A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa
    William A Beltran
    James A Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
    Invest Ophthalmol Vis Sci 47:1669-81. 2006
    ..To characterize the course of retinal disease in X-linked progressive retinal atrophy 2 (XLPRA2), a canine model of early onset X-linked retinitis pigmentosa (XLRP) caused by a two-nucleotide microdeletion in RPGR ORF15...
  49. pmc Altered TGFbeta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency
    Marjolijn Renard
    Center for Medical Genetics, University Hospital Ghent, De Pintelaan 185, Ghent, Belgium
    Eur J Hum Genet 18:895-901. 2010
    ..Glu126Lys and p.Ala397Thr) and compound heterozygosity for missense mutation p.Glu126Val and frameshift mutation c.577delC...
  50. ncbi The genetic determinants of the CYP3A5 polymorphism
    E Hustert
    EPIDAUROS Biotechnologie AG, Bernried, Federal Republic of Germany
    Pharmacogenetics 11:773-9. 2001
    ..q = 0.10). In summary, these results should add to efforts to identify clinically relevant, CYP3A5-specific reactions and to further elucidate traits responsible for variable expression of the entire CYP3A family...
  51. ncbi Frameshift mutation in the V2 domain of human keratin 1 results in striate palmoplantar keratoderma
    Neil V Whittock
    Epithelial Genetics Group, Human Genetics Unit, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
    J Invest Dermatol 118:838-44. 2002
    ..496 at a recombination fraction of 0. Direct sequencing of the keratin 1 gene revealed a frameshift mutation in exon 9 that leads to the partial loss of the glycine loop motif in the V2 domain and the gain of a novel ..
  52. ncbi Mutation spectrum leading to an attenuated phenotype in dystrophinopathies
    Sylvie Tuffery-Giraud
    Laboratoire de Génétique Moleculaire et Chromosomique, CHU de Montpellier, Montpellier, France
    Eur J Hum Genet 13:1254-60. 2005
    ..The results emphasize that mRNA analysis is important in defining Becker mutations and will be of value in assessing various gene therapy strategies...
  53. pmc Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders
    Alberta A H J Thiadens
    Department of Ophthalmology, Erasmus Medical Centre, Rotterdam, The Netherlands
    Am J Hum Genet 85:240-7. 2009
    ..One patient had a frameshift mutation and a splice defect; the other two had a splice defect and a missense variant (p.M455V)...
  54. pmc Escherichia coli frameshift mutation rate depends on the chromosomal context but not on the GATC content near the mutation site
    Mariana A Martina
    Centro de Investigaciones en Quimica Biologica de Cordoba, CIQUIBIC, UNC CONICET, Departamento de Quimica Biologica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Cordoba, Republica Argentina
    PLoS ONE 7:e33701. 2012
    ..In this work we analyzed if the chromosomal context and/or the presence of GATC sites can affect the frameshift mutation rate in the Escherichia coli genome...
  55. ncbi Novel heteroplasmic frameshift and missense somatic mitochondrial DNA mutations in oral cancer of betel quid chewers
    Duan Jun Tan
    Department of Oncology, Georgetown University Medical Center, Washington, DC 20057 1477, USA
    Genes Chromosomes Cancer 37:186-94. 2003
    ..Three were missense mutations (C14F, H186R, T173P) in NADH dehydrogenase subunit 2, and one was a frameshift mutation, 9485delC, in cytochrome c oxidase subunit III...
  56. ncbi An elastin gene mutation producing abnormal tropoelastin and abnormal elastic fibres in a patient with autosomal dominant cutis laxa
    M Tassabehji
    University Department of Medical Genetics and Regional Genetics Service, St Mary s Hospital, Manchester M13 0JH, UK
    Hum Mol Genet 7:1021-8. 1998
    ..A frameshift mutation in exon 32 of the elastin gene is predicted to replace 37 amino acids at the C-terminus of elastin by a ..
  57. ncbi A novel frameshift mutation of POU4F3 gene associated with autosomal dominant non-syndromic hearing loss
    Hee Keun Lee
    Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea
    Biochem Biophys Res Commun 396:626-30. 2010
    ....
  58. pmc Both microsatellite length and sequence context determine frameshift mutation rates in defective DNA mismatch repair
    Heekyung Chung
    Department of Medicine, University of California, San Diego, CA, USA
    Hum Mol Genet 19:2638-47. 2010
    ..To experimentally determine the effect of microsatellite length upon frameshift mutation in gene-specific sequence contexts, we altered the microsatellite length within TGFBR2 exon 3 and ACVR2 ..
  59. pmc Creation and characterization of a renin knockout rat
    Carol Moreno
    Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Hypertension 57:614-9. 2011
    ..ZFN against renin caused a 10-bp deletion in exon 5, resulting in a frameshift mutation. Plasma renin activity was undetectable in the Ren-/- rat, and renin protein was absent from the ..
  60. pmc +1 Frameshifting as a novel mechanism to generate a cryptic cytotoxic T lymphocyte epitope derived from human interleukin 10
    Xavier Saulquin
    INSERM U463, Institut de Biologie, Nantes Cedex 01, France
    J Exp Med 195:353-8. 2002
    ..These observations illustrate the variety of mechanisms leading to generation of cryptic epitopes and suggest that frameshifting in normal cellular genes may be more common than expected...
  61. ncbi Genotype-phenotype correlations in hereditary familial retinoblastoma
    Melissa Taylor
    Service d Oncologie Pediatrique, Institut Curie, Paris, France
    Hum Mutat 28:284-93. 2007
    ..Our analysis suggests in some cases the influence of modifier factors probably involved in mRNA level regulation and/or pRB pathway regulation...
  62. pmc Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome
    Miriam Reuschenbach
    Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany
    Fam Cancer 9:173-9. 2010
    ..Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients...
  63. pmc Identification of an MSI-H tumor-specific cytotoxic T cell epitope generated by the (-1) frame of U79260(FTO)
    Michael Linnebacher
    Department of General, Thoracic, Vascular and Transplant Surgery, University of Rostock, Rostock, Germany
    J Biomed Biotechnol 2010:841451. 2010
    ..Considering the exceptionally high mutation rate of U79260(FTO) in MSI-H colorectal carcinoma (81.8%), this recommends that FSP11 be a component of future vaccines...
  64. pmc Spontaneous frameshift mutations in Saccharomyces cerevisiae: accumulation during DNA replication and removal by proofreading and mismatch repair activities
    C N Greene
    Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, Georgia 30322, USA
    Genetics 159:65-75. 2001
    ..Finally, these analyses suggest that the mismatch repair machinery may be important for generating some classes of frameshift mutations in yeast...
  65. pmc Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3
    Kimia Kahrizi
    Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
    Eur J Hum Genet 19:115-7. 2011
    ..combining array-based exon enrichment and next generation sequencing, we have now identified a homozygous frameshift mutation (c.203dupC; p...
  66. ncbi Long mutant dystrophins and variable phenotypes: evasion of nonsense-mediated decay?
    T P Kerr
    Department of Paediatric Neurology, Guy s Hospital, London, SE1 9RT, UK
    Hum Genet 109:402-7. 2001
    ..We discuss this hypothesis with particular reference to a well-characterised Becker muscular dystrophy patient with a frameshift mutation, where expression of a truncated dystrophin rescues the muscular but not mental phenotype.
  67. ncbi Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease)
    G McKoy
    Department of Cardiological Sciences, St George s Hospital Medical School, London, UK
    Lancet 355:2119-24. 2000
    ..This protein is a key component of desmosomes and adherens junctions, and is important for the tight adhesion of many cell types, including those in the heart and skin...
  68. ncbi Genetack: frameshift identification in protein-coding sequences by the Viterbi algorithm
    Ivan Antonov
    Division of Computational Science and Engineering, Georgia Institute of Technology, 801 Atlantic Drive, Atlanta, Georgia 30332 0280, USA
    J Bioinform Comput Biol 8:535-51. 2010
    ..GeneTack is freely available at http://topaz.gatech.edu/GeneTack/...
  69. pmc Transcriptional profile analysis of RPGRORF15 frameshift mutation identifies novel genes associated with retinal degeneration
    Sem Genini
    Section of Ophthalmology, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Invest Ophthalmol Vis Sci 51:6038-50. 2010
    ..qRT-PCR, Western blot analysis, and immunohistochemistry (IHC) were applied to selected genes, to confirm and expand the microarray results...
  70. pmc Role for topoisomerase 1 in transcription-associated mutagenesis in yeast
    Malcolm J Lippert
    Department of Biology, St Michael s College, Colchester, VT 05439, USA
    Proc Natl Acad Sci U S A 108:698-703. 2011
    ..Given the high degree of conservation between DNA metabolic processes, the links established here among transcription, Top1, and mutagenesis are likely to extend beyond the yeast system...
  71. ncbi Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype
    N Rampino
    The Burnham Institute, La Jolla Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 275:967-9. 1997
    ..These results suggest that inactivating BAX mutations are selected for during the progression of colorectal MMP+ tumors and that the wild-type BAX gene plays a suppressor role in a p53-independent pathway for colorectal carcinogenesis...
  72. ncbi Mutation of a mutL homolog in hereditary colon cancer
    N Papadopoulos
    Johns Hopkins Oncology Center, Baltimore, MD 21231
    Science 263:1625-9. 1994
    ..These results suggest that defects in any of several mismatch repair genes can cause HNPCC...
  73. pmc Analysis of PALB2/FANCN-associated breast cancer families
    Marc Tischkowitz
    Program in Cancer Genetics, Departments of Oncology and Human Genetics and Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada
    Proc Natl Acad Sci U S A 104:6788-93. 2007
    ..The apparently high penetrance noted in this study suggests that at least some PALB2 mutations are associated with a substantially increased risk for the disease...
  74. pmc Regulation of repertoire development through genetic control of DH reading frame preference
    Michael Zemlin
    Department of Pediatrics, Philipps Universitat Marburg, Marburg, Germany
    J Immunol 181:8416-24. 2008
    ..These observations underscore the extent to which the sequence of the D(H) acts to delimit the diversity of the Ab repertoire...
  75. pmc Preferential use of DH reading frame 2 alters B cell development and antigen-specific antibody production
    Robert L Schelonka
    Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    J Immunol 181:8409-15. 2008
    ..These findings indicate that B cell development and Ag-specific Ab production can be heavily influenced by the global amino acid content of the CDR-H3 repertoire...
  76. pmc Same-strand overlapping genes in bacteria: compositional determinants of phase bias
    Niv Sabath
    Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
    Biol Direct 3:36. 2008
    ..We hypothesized that given these two scenarios, the frequencies of initiation and termination codons in the two phases may determine the number for overlapping genes...
  77. ncbi A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse
    N J Charest
    Department of Pediatrics, Yale University, New Haven, Connecticut 06510
    Mol Endocrinol 5:573-81. 1991
    ..testicular feminized (Tfm) mice revealed a single base deletion in the N-terminal domain, resulting in a frameshift mutation. Cycloheximide treatment caused a dramatic increase in AR mRNA in kidneys of Tfm mice, but not wild-type ..
  78. ncbi Asymmetry of frameshift mutagenesis during leading and lagging-strand replication in Escherichia coli
    Damian Gawel
    Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, Warsaw, Poland
    Mutat Res 501:129-36. 2002
    ....
  79. ncbi Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: functional characterization of the 3b protein in pathogenesis and replication
    S Shen
    Institute of Molecular and Cell Biology, National University of Singapore, 117604, Singapore
    Virology 311:16-27. 2003
    ..These results suggest that the 3b gene product is not essential for the replication of IBV...
  80. ncbi A frameshift mutation in the coding region of the myostatin gene (MSTN) affects carcass conformation and fatness in Norwegian White Sheep (Ovis aries)
    I A Boman
    The Norwegian Association of Sheep and Goat Breeders, PO Box 2323, Solli, N 0201 Oslo, Norway
    Anim Genet 40:418-22. 2009
    ..In our material, these MSTN mutations segregated in a pattern showing that they reside in two different haplotypes. The phenotypic effect of the single base deletion is more profound than that of the 3'-UTR mutation...
  81. ncbi Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability
    Min Sung Kim
    Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137 701, South Korea
    Hum Pathol 39:1059-63. 2008
    ..Functionally, colon cancer cells with the frameshift mutation of UVRAG show reduced autophagy formation and increased tumorigenicity...
  82. ncbi Cascading transcriptional effects of a naturally occurring frameshift mutation in Saccharomyces cerevisiae
    Kyle M Brown
    Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Mol Ecol 17:2985-97. 2008
    ..The mutation is a frameshift mutation in a mononucleotide run of eight consecutive T's in the coding region of the gene SSY1, which encodes a key ..
  83. ncbi A homozygous frameshift mutation in BEST1 causes the classical form of Best disease in an autosomal recessive mode
    Hanna Bitner
    Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Invest Ophthalmol Vis Sci 52:5332-8. 2011
    ..The objective was to characterize the molecular and clinical features of patients with the classical form of Best disease that is inherited in an autosomal recessive mode...
  84. pmc Natural selection retains overrepresented out-of-frame stop codons against frameshift peptides in prokaryotes
    Herman Tse
    Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Hong Kong, China
    BMC Genomics 11:491. 2010
    ..Given such a functional significance, we expect statistically overrepresented OSCs in coding sequences as a result of a widespread selection. Accordingly, we examined available prokaryotic genomes to look for evidence of this selection...
  85. ncbi Mutational analysis of the tyrosine phosphatome in colorectal cancers
    Zhenghe Wang
    Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Science 304:1164-6. 2004
    ..These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention...
  86. pmc Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta
    Pablo Lapunzina
    CIBER de Enfermedades Raras, 28046 Madrid, Spain
    Am J Hum Genet 87:110-4. 2010
    ..This finding adds another locus to the spectrum of genes associated with osteogenesis imperfecta and reveals that SP7/OSX also plays a key role in human bone development...
  87. ncbi Clinical and functional effects of mutations in the DAX-1 gene in patients with adrenal hypoplasia congenita
    A T Reutens
    Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Clin Endocrinol Metab 84:504-11. 1999
    ..These studies reveal the variable clinical presentation of DAX-1 mutations and emphasize the value of genetic testing in boys with primary adrenal insufficiency and suspected X-linked AHC...
  88. pmc Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria
    Bugsu Ovunc
    Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Am Soc Nephrol 22:1815-20. 2011
    ..parents with intermittent nephrotic-range proteinuria, we identified a homozygous deleterious frameshift mutation in the gene CUBN, which encodes cubulin, using exome capture and massively parallel re-sequencing...
  89. ncbi Novel mutations in the duplicated region of PKD1 gene
    R Perrichot
    Laboratoire de Genetique Moleculaire, CHU and EFS Bretagne, Brest, France
    Eur J Hum Genet 8:353-9. 2000
    ..In this paper, we also provide a review of the mutations reported so far which are widespread throughout the gene. Although no clear hot spot for mutation is apparent, we will focus on some clustering observed...
  90. ncbi Lack of mismatch correction facilitates genome evolution in mycobacteria
    Burkhard Springer
    Institut fur Medizinische Mikrobiologie, Universitat Zurich, Gloriastrasse 30 32, CH 3028 Zürich, Switzerland
    Mol Microbiol 53:1601-9. 2004
    ..Together, the lack of mismatch correction and a high stringency of initiation of homologous recombination provide an adequate strategy for mycobacterial genome evolution, which occurs by gene duplication and divergent evolution...
  91. ncbi Analysis of PAX6 gene in a Chinese aniridia family
    Hai Yan Zhu
    National Laboratory of Medical Genetics, Xiangya Hospital, Central South University, Changsha 410078, China
    Chin Med J (Engl) 119:1400-2. 2006
  92. pmc Nonsense mediated decay resistant mutations are a source of expressed mutant proteins in colon cancer cell lines with microsatellite instability
    David S Williams
    Epithelial Biochemistry Laboratory, Ludwig Institute for Cancer Research, Melbourne Branch, Parkville, Victoria, Australia
    PLoS ONE 5:e16012. 2010
    ..NMD-resistant transcripts are therefore a likely source of expressed mutant proteins in MSI-High tumours...
  93. ncbi Decreased subunit stability as a novel mechanism for potassium current impairment by a KCNQ2 C terminus mutation causing benign familial neonatal convulsions
    Maria Virginia Soldovieri
    Division of Pharmacology, Department of Neuroscience, University of Naples Federico II, 80131 Naples
    J Biol Chem 281:418-28. 2006
    ..cells, the consequences prompted by a BFNC-causing 1-bp deletion (2043deltaT) in the KCNQ2 gene; this frameshift mutation caused the substitution of the last 163 amino acids of the KCNQ2 C terminus and the extension of the ..
  94. ncbi Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity
    F Rieux-Laucat
    Institut National de la Santé et de la Recherche Médicale INSERM U 429, Hopital Necker Enfants Malades, Paris, France
    Science 268:1347-9. 1995
    ..These findings illustrate the crucial regulatory role of Fas and may provide a molecular basis for some autoimmune diseases in humans...
  95. ncbi Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa
    Miyuki Kawamura
    Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan
    Am J Ophthalmol 137:1137-9. 2004
    ..To determine the frequency and kinds of mutations in the RP1 gene, and to characterize the clinical features of a Japanese family with autosomal dominant retinitis pigmentosa (ADRP) with a novel 2336 to 2337delCT mutation in the RP1 gene...
  96. pmc Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability
    Masakazu Yashiro
    Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan
    BMC Cancer 10:303. 2010
    ..In this study, early stage CRCs were examined for frameshift mutations in these target genes, and compared with late stage tumors and CRC cell lines...
  97. ncbi Loss of MSH3 protein expression is frequent in MLH1-deficient colorectal cancer and is associated with disease progression
    Jens Plaschke
    Department of Surgical Research, Institute of Pathology, Institute of Clinical Genetics, Carl Gustav Carus Hospital, Dresden University of Technology, Dresden, Germany
    Cancer Res 64:864-70. 2004
    ..001), suggesting that MSH3 abrogation may be a predictor of metastatic disease or even favor tumor cell spread in MLH1-deficient colorectal cancers...
  98. ncbi A frameshift mutation in MC4R associated with dominantly inherited human obesity
    G S Yeo
    Nat Genet 20:111-2. 1998
  99. pmc Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature
    Hoa T Truong
    School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia
    BMC Med Genet 11:142. 2010
    ..We expect that as more patients are sequenced for mutations in RAI1, the incidence of frameshift mutations in this hotspot will become more evident...
  100. pmc All three SOS-inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesis
    R Napolitano
    UPR 9003, CNRS Cancerogenese et Mutagenese Moleculaire et Structurale, ESBS and IRCAD, Strasbourg, France
    EMBO J 19:6259-65. 2000
    ..Therefore, in response to the vast diversity of existing DNA damage, the cell uses a pool of 'translesional' DNA polymerases in order to bypass the various DNA lesions...
  101. pmc N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains
    S Santagata
    Ruttenberg Cancer Center, Immunobiology Center, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 97:14572-7. 2000
    ..Taken together, our results suggest a novel mechanism for the development of immunodeficiency in a subset of Omenn's syndrome patients...

Research Grants62

  1. X chromosome cDNA microarray Screening and Functional Study of Novel XLMR genes
    Tao Wang; Fiscal Year: 2009
    ..such as promoter mutations, gene deletions or duplications, and abnormal RNA splicing associated with frameshift mutation and nonsense mutations associated with nonsense-mediated mRNA...
  2. BONE MATRIX AND BONE RESORPTION
    Paul R Odgren; Fiscal Year: 2012
    ..We also showed that a PLEKHM1 frameshift mutation causes osteopetrosis in humans...
  3. Roles of RNA helicase and ribosomal biogenesis in normal and diseased muscle
    Vandana Gupta; Fiscal Year: 2013
    ..identified a 20 base pair deletion in a novel DEAD-box RNA helicase, a RNA binding protein, resulting in a frameshift mutation. Dr...
  4. Transcriptional control of activity-dependent synaptic plasticity
    RICHARD CHESLOCK SANDO; Fiscal Year: 2013
    ..We anticipate that these studies will provide important insight to molecular mechanisms of transcriptional control in neurons, and may eventually facilitate the design of new treatments of neurological diseases. ! ..
  5. Canine Model of Late-Infantile Neuronal Ceroid Lipofuscinosis for Therapy Develop
    Martin L Katz; Fiscal Year: 2010
    ..We discovered Dachshunds that have a frameshift mutation in the canine ortholog of TPP1 and develop a disease very similar to human CLN2...
  6. Crohn's disease-associated NOD2 Mutants
    Xiaojing Ma; Fiscal Year: 2010
    ..We propose to investigate the mechanisms whereby R702W and G908R regulate IL-12/IL-23 gene expression. ..
  7. The Role of SLITRK1 in Tourette and Related Disorders
    Matthew W State; Fiscal Year: 2010
    ..Mutation screening of 204 probands subsequently identified: 1) a truncating frameshift mutation that was present in two affected, and absent in three unaffected family members, and could not be found in ..
  8. Defining the role of Nod2 and bacteria in Atg16L1-dependent intestinal disease.
    KEN HASHIGIWA CADWELL; Fiscal Year: 2013
    ..We will also determine if the Nod2 frameshift mutation (Nod2fs) associated with Crohn's disease is similar or distinct to Nod2 deletion in the presence of ..
  9. Role of renal sodium-phosphate co-transporter NaPI-Iic in phosphate homeostasis
    Clemens Bergwitz; Fiscal Year: 2011
    ..In a large Bedouin kindred affected by HHRH, we recently described a homozygous frameshift mutation (c.228del) in SLC34A3, the gene encoding NaPi-llc (Am J Hum Genetics, 78:179-192, 2006)...
  10. Three new collagen VI genes;COL6A4, COL6A5 and COL6A6
    Jamie Fitzgerald; Fiscal Year: 2013
    ..We identified a homozygous frameshift mutation in COL6A6 that results in a premature stop codon and is predicted to result in the complete absence of a6(..
  11. NEW GENE THERAPY FOR CONNECTIVE TISSUE DISEASES
    Eric Kmiec; Fiscal Year: 1999
    ..In this proposal, we will extend our preliminary results to more clinically relevant protocols by attempting to correct mutations of genomic sequences involved in several inherited connective tissue diseases. ..
  12. NONSENSE RNA SURVEILLANCE IN HEALTH AND DISEASE
    Harry Dietz; Fiscal Year: 2000
    ..Dietz will use a spontaneous frameshift mutation known as gusmps which causes a 200-fold decrease in murine beta-glucuronidase mRNA levels...
  13. The Human Colorectal Instabilitome
    Stephen Meltzer; Fiscal Year: 2007
    ..of MSI-H colorectal cancers and cell lines, in order to identify additional genes targeted by frequent frameshift mutation; 2) To examine functional consequences of mutations in selected coding region targets of microsatellite ..
  14. TRANSFORMATION AND DIFFERENTIATION BY V AND C ABL GENES
    E Reddy; Fiscal Year: 1992
    ..Following the purification of the recombinant proteins, we propose to carry out experiments aimed at understanding the biochemical differences between normal and transforming abl proteins...
  15. Homologous recombination in Xenopus and Zebrafish
    Sigrid Reinsch; Fiscal Year: 2005
    ..will be used target a GFP transgene to alter the expression of GFP expression through coding changes, frameshift mutation, or stop codon insertion...
  16. The Functional analysis of the novel protein spartin.
    JOANNA BAKOWSKA; Fiscal Year: 2009
    ..syndrome is a "complex" form of an autosomal recessive hereditary spastic paraplegia that results from a frameshift mutation in the spartin gene, SPG20...
  17. Models of X-Linked Retinitis Pigmentosa
    GUSTAVO AGUIRRE; Fiscal Year: 2007
    ..mutation (XLPRA1) is caused by loss of function requiring gene replacement; and b) -that disease from the frameshift mutation (XLPRA2) arises from a deleterious gain of function, necessitating early intervention with combined ..
  18. Molecular Studies on Transactivation Potential of PAX9
    Hitesh Kapadia; Fiscal Year: 2006
    ..We recently identified a novel frameshift mutation (793InsC) in the COOH-terminal domain (exon 4) of PAX9 in members of a large family with congenitally ..
  19. Large Animal Model of Macular Degeneration
    ROBERT PETTERS; Fiscal Year: 2005
    ..Studies of pigs transgenic for ELOVL4 should lead to new insights into lipid metabolism in photoreceptor cells and may reveal a novel pathway in the pathogenesis of macular degeneration. ..
  20. GENETIC CONTROL OF BB RAT AUTOIMMUNITY
    Ake Lernmark; Fiscal Year: 2009
    ..Our discovery in 2002 of the frameshift mutation in Ian5 (IAN4L1) that results in lymphopenia uncovered a previously unknown family of Ian genes that appear ..
  21. CELL BIOLOGY OF SURFACTANT PROTEIN B (SP B)
    Daphne Demello; Fiscal Year: 2000
    ..In the first ten infants studied we identified two mutations in the SP-B gene - the more common, a frameshift mutation - 121ins2, or a 3' splice junction deletion (delta Ex 4) (J Pediatr: 125:43-50, 1994)...
  22. DNA REPAIR IN DRUG RESISTANCE MUTATION
    Susan Rosenberg; Fiscal Year: 2003
    ..The first is from work on stationary-phase ("adaptive") reversion of an episomal lac frameshift mutation in E. coli...
  23. Role of titin in heart function and disease
    Henk Granzier; Fiscal Year: 2007
    ..We will test the hypothesis that titin's M-line region is critically important for the structural integrity of contracting sarcomere. [unreadable] [unreadable]..
  24. Mechanisms of Adaptive Amplification
    Philip J Hastings; Fiscal Year: 2010
    ....
  25. PKA & PKC REGULATION OF NT2-N & RECOMBINANT GABARS
    Robert MacDonald; Fiscal Year: 2003
    ..7) The NT2 and NT2-N GABAR subtype protein phosphorylated by PKA and PKC. 8) The biophysical mechanisms PKA and PKC modification of NT2 and NT2-N GABAR currents. ..
  26. Canine model for assessing CNS access P-gp substrates
    KATRINA MEALEY; Fiscal Year: 2005
    ....
  27. GABAA RECEPTOR CHANNEL ALTERATION BY PROLONGED SEIZURES
    Robert MacDonald; Fiscal Year: 2003
    ....
  28. DNA replication, DNA repair and microsatellite stability
    Kristin Eckert; Fiscal Year: 2009
    ..Microsatellite allele lengths can directly affect gene expression. As microsatellites are polymorphic in human populations, this effect on gene regulation may be an important factor contributing to individual cancer risk. ..
  29. MUTATIONAL MECHANISMS OF REPETITIVE DNA IN HUMAN CELLS
    Kristin Eckert; Fiscal Year: 2001
    ..Our long-term research objective is to test the hypothesis that mutations in repetitive DNA provide an important source of genotypic variation that drives neoplastic progression. ..
  30. Error Prone DNA Synthesis and Oncogene Mutagensis
    Bernard Strauss; Fiscal Year: 2004
    ..Blocking the action of the error-prone polymerases should not stop replication. However, mutational cascades, such as those leading to tumor drug resistance, should be inhibited by such a block. ..
  31. SPONTANEOUS AND CARCINOGEN-INDUCED MUTAGENESIS
    Jeffrey H Miller; Fiscal Year: 2010
    ..coli, and also that would complement different E. coli repair defects. We will also construct a system for studying mutagenesis in a pathogen such as B. pertussis. ..
  32. Repair of Clustered DNA Damages
    Yoke W Kow; Fiscal Year: 2010
    ..In addition, it will provide significant insight as to the potential mechanism involved in melanoma progression. ..
  33. THE ROLE OF RB IN THE RETINA & OTHER TISSUES
    JAMES HARBOUR; Fiscal Year: 2009
    ..Consequently, these aims are highly relevant to the vision statement of the NEI, and they address several major program goals and objectives of the Retinal Diseases Program. ..
  34. PROTEIN 4.1 TUMOR SUPPRESSORS IN MENINGIOMA PATHOGENESIS
    David Gutmann; Fiscal Year: 2003
    ..and (3) analyzing the ability of DAL-1 to impair cell growth and motility. These studies are collectively designed to define the role of this novel family of growth regulators in meningioma tumorigenesis and progression. ..
  35. mRNA Export Regulation in adenovirus-Infected Cells
    SARAH FLINT; Fiscal Year: 2003
    ..abstract_text> ..
  36. PREDISPOSING/MODIFYING GENES IN HEREDITARY COLON CANCER
    Paivi Peltomaki; Fiscal Year: 2001
    ..The aim is to identify genes that might modify the clinical phenotype of HNPCC, taking advantage of association and linkage-based approaches in these genetically homogeneous subsets of HNPCC patients. ..
  37. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 2003
    ..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
  38. GENETICS OF NEUROPEPTIDE Y FUNCTION
    RICHARD PALMITER; Fiscal Year: 2001
    ..These genetic experiments should help rationalize the current disparate results obtained by permanent NPY gene silencing and by acute intervention of NPY signaling. ..
  39. Tenth Small Genomes Conference-2002
    Jeffrey Miller; Fiscal Year: 2002
    ....
  40. ANALYSIS OF THE MURINE ANTIBODY REPERTOIRE
    GARNETT H KELSOE; Fiscal Year: 2010
    ..Qom cap mop axiom 0-c 0opccc woo'- t00 0co -td ..
  41. Molecular Determinants of Neural Stem Cell Function
    David Gutmann; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  42. Antisense Mediated Suppression of Dystrophin Mutations
    Michael Howard; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  43. MOLECULAR GENETICS OF NAIL PATELLA SYNDROME
    Iain McIntosh; Fiscal Year: 2004
    ..Furthermore, by identification of elements controlling LMX1B expression and the factors interacting with LMX1B, a better model of limb development will be derived. ..
  44. GENE EXPRESSION IN LIMB GIRDLE MUSCULAR DYSTROPHY
    Elizabeth McNally; Fiscal Year: 2004
    ..Together, these experiments will outline the temporal profile of gene expression changes that arise in these disorders. ..
  45. CONFERENCE PROPOSAL: CILIATE MOLECULAR BIOLOGY
    LAWRENCE KLOBUTCHER; Fiscal Year: 2003
    ..abstract_text> ..
  46. Methods in Protein Structure Analysis 2004
    Carl Anderson; Fiscal Year: 2004
    ..The overall aim is to provide a forum for exchanging the latest methods and ideas in protein structure analysis and proteomics to current and future practitioners. ..
  47. TWO X-LINKED GENES THAT REGULATE MINERAL HOMEOSTASIS
    Michael Whyte; Fiscal Year: 2002
    ....
  48. Consequences of generalized lack of GHRH
    Roberto Salvatori; Fiscal Year: 2005
    ..By recombinase technique, we will generate KO lines with no Neor, avoiding any interference with distant or neighboring genes. In addition, results obtained in the GHRHKO1 line will be confirmed or disproved. ..
  49. Identify Waardenburg syndrome type 2 loci in man
    JEFFREY MILUNSKY; Fiscal Year: 2005
    ..We will perform a high-density genome scan coupled with linkage disequilibrium analyses on 3 large multigenerational families and multiple smaller families with WS2 to identify candidate gene(s) with mutations causing WS2. ..
  50. GENETIC VARIATION IN HUMAN NHEJ DNA REPAIR GENES
    Carl Anderson; Fiscal Year: 2005
    ..This study also will provide a moderately dense set of mapped polymorphic markers within the five know NHEJ genes for subsequence linkage studies that could reveal subtle effects and more complex allele interactions. ..
  51. Neurofibromatosis Foundation International Consortium
    David Gutmann; Fiscal Year: 2003
    ..abstract_text> ..
  52. The Molecular Basis of Juvenile Polyposis
    James Howe; Fiscal Year: 2005
    ..These studies will also benefit JP patients by improving presymptomatic genetic testing, and identification of new therapeutic targets for polyp regression and cancer prevention in JP. ..
  53. Mechanisms of Disease in the Newborn Human Infant
    F Cole; Fiscal Year: 2006
    ..As such, this program should provide for new pediatric scholars to lead the way for future advances in this important area of child health. ..
  54. TRANSCRIPTIONAL REGULATION OF ADENOVIRUS LATE GENES
    SARAH FLINT; Fiscal Year: 2007
    ..The possibility that a novel mechanism regulates the rate at which the viral replication proteins are produced will also be assessed by genetic methods. ..
  55. Identification and Preclinical Evaluation of New Brain Tumor Therapies
    David Gutmann; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  56. GENOMICS OF HIGH TEMPERATURE BIOLOGICAL SYSTEMS
    Jeffrey Miller; Fiscal Year: 2005
    ..We have begun an indepth investigation of the repair systems in this organism, and we will continue to characterize DNA repair strategies and proteins. ..
  57. Structure of Eukaryotic Translation Elongation Factor 1
    TERRI KINZY; Fiscal Year: 2004
    ..With S. cerevisiae, the structural information obtained on eEF1A can be utilized for molecular genetic analysis of the critical residues for function and regulation. ..
  58. Role of Pro-opiomelanocortin mutations in human obesity
    Christian Vaisse; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  59. Peroxisome Membrane Biogenesis
    Stephen Gould; Fiscal Year: 2004
    ..abstract_text> ..