mutation

Summary

Summary: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Top Publications

  1. ncbi Basic local alignment search tool
    S F Altschul
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894
    J Mol Biol 215:403-10. 1990
  2. pmc One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products
    K A Datsenko
    Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
    Proc Natl Acad Sci U S A 97:6640-5. 2000
  3. pmc The genetics of Caenorhabditis elegans
    S Brenner
    Genetics 77:71-94. 1974
  4. pmc A map of human genome variation from population-scale sequencing
    Richard M Durbin
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK
    Nature 467:1061-73. 2010
  5. pmc COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
    Simon A Forbes
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA Cambridge, UK
    Nucleic Acids Res 39:D945-50. 2011
  6. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
  7. ncbi EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
    J Guillermo Paez
    Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 304:1497-500. 2004
  8. pmc Intratumor heterogeneity and branched evolution revealed by multiregion sequencing
    Marco Gerlinger
    Cancer Research UK London Research Institute, London, United Kingdom
    N Engl J Med 366:883-92. 2012
  9. doi The genetic landscape of a cell
    Michael Costanzo
    Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
    Science 327:425-31. 2010
  10. pmc Core signaling pathways in human pancreatic cancers revealed by global genomic analyses
    Sian Jones
    Sol Goldman Pancreatic Cancer Research Center, Ludwig Center and Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1801-6. 2008

Detail Information

Publications298 found, 100 shown here

  1. ncbi Basic local alignment search tool
    S F Altschul
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894
    J Mol Biol 215:403-10. 1990
    ..In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity...
  2. pmc One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products
    K A Datsenko
    Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA
    Proc Natl Acad Sci U S A 97:6640-5. 2000
    ..This procedure should be widely useful, especially in genome analysis of E. coli and other bacteria because the procedure can be done in wild-type cells...
  3. pmc The genetics of Caenorhabditis elegans
    S Brenner
    Genetics 77:71-94. 1974
    ..Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic ..
  4. pmc A map of human genome variation from population-scale sequencing
    Richard M Durbin
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK
    Nature 467:1061-73. 2010
    ..These methods and public data will support the next phase of human genetic research...
  5. pmc COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
    Simon A Forbes
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA Cambridge, UK
    Nucleic Acids Res 39:D945-50. 2011
    ..With all genomic information recently updated to GRCh37, COSMIC integrates many diverse types of mutation information and is making much closer links with Ensembl and other data resources.
  6. pmc An integrated genomic analysis of human glioblastoma multiforme
    D Williams Parsons
    Ludwig Center for Cancer Genetics and Therapeutics, and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1807-12. 2008
    ..These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs...
  7. ncbi EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
    J Guillermo Paez
    Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 304:1497-500. 2004
    ..These results suggest that EGFR mutations may predict sensitivity to gefitinib...
  8. pmc Intratumor heterogeneity and branched evolution revealed by multiregion sequencing
    Marco Gerlinger
    Cancer Research UK London Research Institute, London, United Kingdom
    N Engl J Med 366:883-92. 2012
    ..Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples...
  9. doi The genetic landscape of a cell
    Michael Costanzo
    Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
    Science 327:425-31. 2010
    ..We also demonstrate that extensive and unbiased mapping of the genetic landscape provides a key for interpretation of chemical-genetic interactions and drug target identification...
  10. pmc Core signaling pathways in human pancreatic cancers revealed by global genomic analyses
    Sian Jones
    Sol Goldman Pancreatic Cancer Research Center, Ludwig Center and Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 321:1801-6. 2008
    ..Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.
  11. pmc Human non-synonymous SNPs: server and survey
    Vasily Ramensky
    European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nucleic Acids Res 30:3894-900. 2002
    ..The strongest selective pressure was detected for proteins involved in transcription regulation...
  12. ncbi Initial sequencing and analysis of the human genome
    E S Lander
    Whitehead Institute for Biomedical Research, Center for Genome Research, Cambridge, MA 02142, USA
    Nature 409:860-921. 2001
    ..We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence...
  13. pmc The mutational landscape of head and neck squamous cell carcinoma
    Nicolas Stransky
    The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
    Science 333:1157-60. 2011
    ..More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms...
  14. pmc The cancer genome
    Michael R Stratton
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
    Nature 458:719-24. 2009
    ..These studies will provide us with a detailed and comprehensive perspective on how individual cancers have developed...
  15. ncbi Stem cells, cancer, and cancer stem cells
    T Reya
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, California 94305, USA
    Nature 414:105-11. 2001
    ....
  16. pmc VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing
    Daniel C Koboldt
    The Genome Institute, Washington University, St Louis, MO 63108, USA
    Genome Res 22:568-76. 2012
    Cancer is a disease driven by genetic variation and mutation. Exome sequencing can be utilized for discovering these variants and mutations across hundreds of tumors...
  17. ncbi Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
    Hannah Farmer
    Cancer Research UK Gene Function and Regulation Group, London, UK
    Nature 434:917-21. 2005
    ..These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer...
  18. pmc Exome sequencing identifies the cause of a mendelian disorder
    Sarah B Ng
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    Nat Genet 42:30-5. 2010
    ..Exome sequencing of a small number of unrelated affected individuals is a powerful, efficient strategy for identifying the genes underlying rare mendelian disorders and will likely transform the genetic analysis of monogenic traits...
  19. pmc Inhibition of mutated, activated BRAF in metastatic melanoma
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, USA
    N Engl J Med 363:809-19. 2010
    ..The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease...
  20. ncbi Cancer genes and the pathways they control
    Bert Vogelstein
    Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Nat Med 10:789-99. 2004
    ..The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation...
  21. pmc Patterns of somatic mutation in human cancer genomes
    Christopher Greenman
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Nature 446:153-8. 2007
    ..Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated...
  22. ncbi The complete genome sequence of Escherichia coli K-12
    F R Blattner
    Laboratory of Genetics, University of Wisconsin Madison, 445 Henry Mall, Madison, WI 53706, USA
    Science 277:1453-62. 1997
    ..The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer...
  23. doi Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer
    Eric Van Cutsem
    University Hospital Gasthuisberg, Digestive Oncology Unit, Herestraat 49, 3000 Leuven, Belgium
    N Engl J Med 360:1408-17. 2009
    ..cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer and sought associations between the mutation status of the KRAS gene in tumors and clinical response to cetuximab.
  24. pmc Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1
    Nishant Agrawal
    Department of Otolaryngology Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Science 333:1154-7. 2011
    ..Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type...
  25. doi Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma
    Tony S Mok
    State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong
    N Engl J Med 361:947-57. 2009
    ..Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer...
  26. pmc Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma
    Houtan Noushmehr
    USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA
    Cancer Cell 17:510-22. 2010
    ..Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds...
  27. ncbi Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC
    P J Morin
    Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 275:1787-90. 1997
    ..These results indicate that regulation of beta-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or beta-catenin...
  28. pmc Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
    Brandon F Keele
    Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35223, USA
    Proc Natl Acad Sci U S A 105:7552-7. 2008
    ....
  29. pmc EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib
    William Pao
    Program in Cancer Biology and Genetics and Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 101:13306-11. 2004
    ..003). Because most mutation-positive tumors were adenocarcinomas from patients who smoked <100 cigarettes in a lifetime ("never smokers"), ..
  30. pmc Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer
    Eunice L Kwak
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    N Engl J Med 363:1693-703. 2010
    ..We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase...
  31. doi Genome evolution and adaptation in a long-term experiment with Escherichia coli
    Jeffrey E Barrick
    Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA
    Nature 461:1243-7. 2009
    ..This same population later evolved an elevated mutation rate and accumulated hundreds of additional mutations dominated by a neutral signature...
  32. pmc Sequence analysis of mutations and translocations across breast cancer subtypes
    Shantanu Banerji
    The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Nature 486:405-9. 2012
    ..The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor...
  33. pmc Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
    Xose S Puente
    Departamento de Bioquimica y Biologia Molecular, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nature 475:101-5. 2011
    ..The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 ..
  34. pmc Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
    Gideon Bollag
    Plexxikon Inc, 91 Bolivar Drive, Berkeley, California 94710, USA
    Nature 467:596-9. 2010
    ..These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity...
  35. pmc Coding-sequence determinants of gene expression in Escherichia coli
    Grzegorz Kudla
    Department of Biology and Program in Applied Mathematics and Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 324:255-8. 2009
    ..In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness...
  36. pmc Melanoma genome sequencing reveals frequent PREX2 mutations
    Michael F Berger
    The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
    Nature 485:502-6. 2012
    ..A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the ..
  37. ncbi Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae
    A L Goldstein
    Department of Microbiology, 3020 Duke University Medical Center, Durham, NC 27710, USA
    Yeast 15:1541-53. 1999
    ..These attributes make the cassettes ideally suited for creating S. cerevisiae strains with multiple mutations within a single strain...
  38. ncbi A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia
    George Adrian Calin
    Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA
    N Engl J Med 353:1793-801. 2005
    ..We investigated whether microRNA profiles are associated with known prognostic factors in CLL...
  39. ncbi Requirement for p53 and p21 to sustain G2 arrest after DNA damage
    F Bunz
    The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 282:1497-501. 1998
    ..Thus, p53 and p21 appear to be essential for maintaining the G2 checkpoint in human cells...
  40. pmc Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, USA
    N Engl J Med 367:1694-703. 2012
    ..To address this problem, we conducted a phase 1 and 2 trial of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MAPK kinase (MEK) inhibitor...
  41. pmc A comprehensive catalogue of somatic mutations from a human cancer genome
    Erin D Pleasance
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:191-6. 2010
    ..The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
  42. doi Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR
    Makoto Maemondo
    Miyagi Cancer Center, Miyagi, Japan
    N Engl J Med 362:2380-8. 2010
    ....
  43. pmc Tandem repeats finder: a program to analyze DNA sequences
    G Benson
    Department of Biomathematical Sciences, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    Nucleic Acids Res 27:573-80. 1999
    ..These sequences range in size from 3 kb up to 700 kb. A World Wide Web server interface atc3.biomath.mssm.edu/trf.html has been established for automated use of the program...
  44. ncbi PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
    J Li
    Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA
    Science 275:1943-7. 1997
    ..These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions...
  45. pmc Analysis of genetic inheritance in a family quartet by whole-genome sequencing
    Jared C Roach
    Institute for Systems Biology, Seattle, WA 98103, USA
    Science 328:636-9. 2010
    ..We also directly estimated a human intergeneration mutation rate of approximately 1.1 x 10(-8) per position per haploid genome...
  46. doi Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study
    Jean Yves Douillard
    Centre Rene Gauducheau, Nantes, France
    J Clin Oncol 28:4697-705. 2010
    ....
  47. ncbi A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase
    P Frosst
    Nat Genet 10:111-3. 1995
    ..We have identified a common mutation in MTHFR which alters a highly-conserved amino acid; the substitution occurs at a frequency of approximately 38% ..
  48. ncbi Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
    R E Amir
    Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Genet 23:185-8. 1999
    ..As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males...
  49. ncbi Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer
    Manabu Soda
    Division of Functional Genomics, Jichi Medical University, Tochigi 329 0498, Japan
    Nature 448:561-6. 2007
    ..Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC...
  50. pmc The clonal and mutational evolution spectrum of primary triple-negative breast cancers
    Sohrab P Shah
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada
    Nature 486:395-9. 2012
    ..Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes...
  51. pmc Synonymous but not the same: the causes and consequences of codon bias
    Joshua B Plotkin
    Department of Biology and Program in Applied Mathematics and Computational Science, University of Pennsylvania, 433 South University Avenue, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 12:32-42. 2011
    ..Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts...
  52. pmc Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation
    Maria E Figueroa
    Weill Cornell Medical College, New York, NY 10065, USA
    Cancer Cell 18:553-67. 2010
    ..Finally, either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic differentiation and increased stem/progenitor cell marker expression, suggesting a shared proleukemogenic effect...
  53. pmc Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
    Ignacio Varela
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 469:539-42. 2011
    ..4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology...
  54. pmc Patterns and rates of exonic de novo mutations in autism spectrum disorders
    Benjamin M Neale
    Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 485:242-5. 2012
    ..Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate...
  55. pmc Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1
    Roel G W Verhaak
    The Eli and Edythe L Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
    Cancer Cell 17:98-110. 2010
    ..We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies...
  56. pmc Disease-specific induced pluripotent stem cells
    In Hyun Park
    Department of Medicine, Division of Pediatric Hematology Oncology, Children s Hospital Boston, and Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cell 134:877-86. 2008
    ..Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development...
  57. ncbi IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes...
  58. doi Diverse somatic mutation patterns and pathway alterations in human cancers
    Zhengyan Kan
    Department of Molecular Biology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 466:869-73. 2010
    ..We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes...
  59. ncbi CRISPR provides acquired resistance against viruses in prokaryotes
    Rodolphe Barrangou
    Danisco USA Inc, 3329 Agriculture Drive, Madison, WI 53716, USA
    Science 315:1709-12. 2007
    ..Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity...
  60. pmc De novo mutations revealed by whole-exome sequencing are strongly associated with autism
    Stephan J Sanders
    Program on Neurogenetics, Child Study Center, Department of Psychiatry, Yale University School of Medicine, 230 South Frontage Road, New Haven, Connecticut 06520, USA
    Nature 485:237-41. 2012
    ..On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in ..
  61. pmc Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing
    Marcin Imielinski
    Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA
    Cell 150:1107-20. 2012
    ..These analyses revealed a mean exonic somatic mutation rate of 12...
  62. ncbi High frequency of mutations of the PIK3CA gene in human cancers
    Yardena Samuels
    Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Science 304:554. 2004
  63. pmc McKusick's Online Mendelian Inheritance in Man (OMIM)
    Joanna Amberger
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Nucleic Acids Res 37:D793-6. 2009
    ..Approximately 70 new entries are added and 700 entries are updated per month. OMIM is expanding content and organization in response to shifting biological paradigms and advancing biotechnology...
  64. ncbi alpha-Synuclein locus triplication causes Parkinson's disease
    A B Singleton
    Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 302:841. 2003
  65. doi Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial
    Rafael Rosell
    Catalan Institute of Oncology, Badalona, Spain
    Lancet Oncol 13:239-46. 2012
    ..We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC.
  66. pmc DNMT3A mutations in acute myeloid leukemia
    Timothy J Ley
    Department of Genetics, Genome Center, Washington University, St Louis, MO 63110, USA
    N Engl J Med 363:2424-33. 2010
    ..The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown...
  67. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
    ..Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA...
  68. pmc Genome remodelling in a basal-like breast cancer metastasis and xenograft
    Li Ding
    The Genome Center at Washington University, St Louis, Missouri 63108, USA
    Nature 464:999-1005. 2010
    ..The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis...
  69. doi Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial
    Tetsuya Mitsudomi
    Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa ku, Nagoya, Japan
    Lancet Oncol 11:121-8. 2010
    ..However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain.
  70. ncbi Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
    D R Rosen
    Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Charlestown 02129
    Nature 362:59-62. 1993
    ..Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families...
  71. pmc Improved survival with vemurafenib in melanoma with BRAF V600E mutation
    Paul B Chapman
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    N Engl J Med 364:2507-16. 2011
    Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation.
  72. doi Advances in understanding cancer genomes through second-generation sequencing
    Matthew Meyerson
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nat Rev Genet 11:685-96. 2010
    ..This Review focuses on the methodological considerations for characterizing somatic genome alterations in cancer and the future prospects for these approaches...
  73. pmc PI3K pathway alterations in cancer: variations on a theme
    T L Yuan
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 2115, USA
    Oncogene 27:5497-510. 2008
    ..In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions...
  74. pmc Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
    Ramin Nazarian
    Division of Dermatology Department of Medicine, UCLA s Jonsson Comprehensive Cancer Center, 52 121 CHS, Los Angeles, California 90095 1750, USA
    Nature 468:973-7. 2010
    ....
  75. pmc Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
    Lenny Dang
    Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA
    Nature 462:739-44. 2009
    ..These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas...
  76. pmc Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib
    Jeffrey A Sosman
    Vanderbilt Ingram Cancer Center, Nashville, TN 37232 6307, USA
    N Engl J Med 366:707-14. 2012
    ..The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial...
  77. pmc A small-cell lung cancer genome with complex signatures of tobacco exposure
    Erin D Pleasance
    Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Nature 463:184-90. 2010
    Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA...
  78. doi Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
    Sohrab P Shah
    Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
    Nature 461:809-13. 2009
    ..Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression...
  79. pmc Highly recurrent TERT promoter mutations in human melanoma
    Franklin W Huang
    Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
    Science 339:957-9. 2013
    ..Thus, somatic mutations in regulatory regions of the genome may represent an important tumorigenic mechanism...
  80. ncbi Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation
    M E Gurney
    Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
    Science 264:1772-5. 1994
    ..The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS...
  81. pmc IDH1 and IDH2 mutations in gliomas
    Hai Yan
    Department of Pathology, Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA
    N Engl J Med 360:765-73. 2009
    ....
  82. ncbi Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
    Thomas J Lynch
    Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA
    N Engl J Med 350:2129-39. 2004
    ..However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown...
  83. pmc The landscape of cancer genes and mutational processes in breast cancer
    Philip J Stephens
    Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
    Nature 486:400-4. 2012
    ..The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational ..
  84. doi The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
    James W Vardiman
    Department of Pathology, University of Chicago, IL, USA
    Blood 114:937-51. 2009
    ....
  85. pmc p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
    Geir Bjørkøy
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Cell Biol 171:603-14. 2005
    ..We suggest that p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery...
  86. pmc Mutational processes molding the genomes of 21 breast cancers
    Serena Nik-Zainal
    Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Cell 149:979-93. 2012
    All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed...
  87. ncbi Complete replication of hepatitis C virus in cell culture
    Brett D Lindenbach
    Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 309:623-6. 2005
    ..HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals...
  88. ncbi The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults
    B Lemaitre
    Institut de Biologie Moléculaire at Cellulaire, UPR 9022 du Centre National de la Recherche Scientifique, Strasbourg, France
    Cell 86:973-83. 1996
    ..Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways...
  89. pmc Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning
    Shawn J Cokus
    Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA
    Nature 452:215-9. 2008
    ....
  90. pmc Somatic mutations affect key pathways in lung adenocarcinoma
    Li Ding
    The Genome Center at Washington University, Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63108, USA
    Nature 455:1069-75. 2008
    ..Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment...
  91. doi Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers
    Elgene Lim
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    Nat Med 15:907-13. 2009
    ..To explore early cellular changes that occur in BRCA1 mutation carriers, we have prospectively isolated distinct epithelial subpopulations from normal mammary tissue and ..
  92. pmc Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations
    Kaya Bilguvar
    Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nature 467:207-10. 2010
    ..These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging...
  93. doi Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
    Jeremy Schwartzentruber
    McGill University and Genome Quebec Innovation Centre, Montreal, Quebec H3A 1A4, Canada
    Nature 482:226-31. 2012
    ..3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX ..
  94. doi Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
    Caicun Zhou
    Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
    Lancet Oncol 12:735-42. 2011
    ..The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.
  95. ncbi Not so different after all: a comparison of methods for detecting amino acid sites under selection
    Sergei L Kosakovsky Pond
    Antiviral Research Center, University of California San Diego, USA
    Mol Biol Evol 22:1208-22. 2005
    ..We demonstrate our methods on sequence data from the human immunodeficiency virus type 1 env and pol genes and simulated alignments...
  96. pmc De novo gene disruptions in children on the autistic spectrum
    Ivan Iossifov
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Neuron 74:285-99. 2012
    ..We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders...
  97. ncbi Identification of c-MYC as a target of the APC pathway
    T C He
    Howard Hughes Medical Institute and Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA
    Science 281:1509-12. 1998
    ..These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers...
  98. doi Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis
    Wendy De Roock
    Centre for Human Genetics, KU Leuven, Leuven, Belgium
    Lancet Oncol 11:753-62. 2010
    ....

Research Grants79

  1. Genetic variation and regulatory networks: Mechanisms and complexity
    DANA PE ER; Fiscal Year: 2009
    ..These tools will be made publicly available, including a friendly graphical user interface and visualization. ..
  2. Variation in M. tuberculosis in response to host selection
    Sarah Fortune; Fiscal Year: 2009
    ..In these studies, we expect to provide fundamental insights into the mechanisms and targets of diversifying immune selection in M. tuberculosis. ..
  3. NIH Director's Pioneer Award
    ERICH JARVIS; Fiscal Year: 2009
    ..Repairing the pathway in vocal learners, when damaged, would have profound impact for correcting neurological disorders of speech. ..
  4. Pathogenesis and Treatment of Liver Disease in Transaldolase Deficiency
    Andras Perl; Fiscal Year: 2013
    ..We created an animal model of TAL deficiency by a targeted genetic mutation in the mouse...
  5. Cystathionine beta synthase (CBS) and angiogenesis
    Priyabrata Mukherjee; Fiscal Year: 2013
    ..Therefore, impairment of the transsulfuration pathway via pharmacological inhibition or genetic deletion/mutation of CBS may lead to, a) hyperhomocysteninemia (HHcy);b) reduction in cellular glutathione GSH level due to lack of ..
  6. Regulation of B Cell Function by Membrane-Cytoskeletal Remodeling
    Neetu Gupta; Fiscal Year: 2012
    ..A phosphomimetic mutation of T567 to aspartate that holds ezrin in an open conformation, results in inhibition of BCR-dependent membrane ..
  7. Epigenetic mechanisms relevant to the pathogenesis of ALS
    Neil W Kowall; Fiscal Year: 2013
    ..stress in vitro;2) To determine the role of LSD1 in the survival of motor neurons harboring the G93A SOD1 mutation;and 3) To investigate the therapeutic effect of LSD1 modulators on motor neuron degeneration, neuropathology, ..
  8. Med1 in Liver Metabolism, Regeneration and Cancer
    Janardan K Reddy; Fiscal Year: 2013
    ..Studies with conditional Med1 null mutation have established that Med1 is required for fatty acid oxidation and glucose metabolism...
  9. Genetic and physiological causes of inherited Vascular and Metabolic Diseases
    Arya Mani; Fiscal Year: 2013
    ..The mutation, substitutes cysteine for arginine (R611C) at a highly conserved residue of the second epidermal growth factor ..
  10. REGULATION AND FUNCTION OF STE20-RELATED PROTEIN KINASES
    Melanie H Cobb; Fiscal Year: 2012
    ..in either WNK1 or WNK4 cause pseudohypoaldosteronism type II (PHA II), a form of high blood pressure caused by mutation of a single gene...
  11. Cellular &Molecular Defects in Human B Cell Development
    Charlotte Cunningham-Rundles; Fiscal Year: 2013
    ..B cells of patients lack the capacity for normal somatic hyper-mutation and isotype switch, secrete immune globulins poorly, and fail to differentiate into plasma cells...
  12. 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...
  13. Role of Diabetes in Development of Renal Cell Carcinoma
    SAMY LEWIZ HABIB; Fiscal Year: 2013
    ..In addition, we found that mutation in Ser326, the active site of OGG1 enzyme is increased in DNA blood samples from diabetic patients...
  14. Model of Timothy Syndrome to Screen Drugs with Induced Pluripotent Stem Cells
    Masayuki Yazawa; Fiscal Year: 2013
    ..Here I propose to study a missense mutation in the L-type Ca2+ channel, CaV1...
  15. Model of Timothy Syndrome to Screen Drugs with Induced Pluripotent Stem Cells
    Masayuki Yazawa; Fiscal Year: 2013
    ..Here I propose to study a missense mutation in the L-type Ca2+ channel, CaV1...
  16. BONE MATRIX AND BONE RESORPTION
    Paul R Odgren; Fiscal Year: 2012
    ..Aim 1 grows from our previous work which found the causative mutation in the osteopetrotic incisors absent (ia) rat in a novel gene, Plekhm1...
  17. Regulation of Cell Signaling by Human Biliverdin Reductase
    Mahin D Maines; Fiscal Year: 2013
    ..Biliverdin is a modulator of liver tumor cell growth, AhR ligand, and is elevated in carriers of BVR mutation with end-stage liver cirrhosis...
  18. Mechanisms of Sex Determination in Zebrafish
    JOHN HARVEY POSTLETHWAIT; Fiscal Year: 2013
    ..to die in some individuals and to survive in others? An important tool to probe this question is a recessive mutation in fancl that causes female-to-male sex reversal...
  19. The genetics and pathophysiology of impaired Wnt signaling in metabolic syndrome
    Arya Mani; Fiscal Year: 2012
    ..These findings have established a causal link between Wnt signaling impairment caused by LRP6 mutation and metabolic syndrome and raises the possibility of complex downstream effects of the mutation which warrant ..
  20. Genetic Studies of Optic Atrophy
    Taosheng Huang; Fiscal Year: 2012
    Optic atrophy gene 1 (OPA1) is a nuclear gene encoding a mitochondrial protein. Mutation of OPA1 is the most common cause for autosomal dominant optic atrophy (DOA)...
  21. Environmental Risk Factors for Copy Number Variation in Human Chromosomes
    THOMAS EDWARD WILSON; Fiscal Year: 2010
    ..and developmental disorders have found de novo CNVs in 5-17% of affected individuals, suggesting a high mutation rate...
  22. 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...
  23. Iron-Induced Changes in Liver That Predispose to Malignancy
    Harriet C Isom; Fiscal Year: 2010
    ..Oxidative stress is induced resulting in oxidative damage to DNA. This setting gives way to mutation and other DNA aberrations that accumulate with time...
  24. Integrated signaling of eicosanoids in HSC formation and regeneration
    Trista E North; Fiscal Year: 2013
    ..The transcription factor Runx1, a frequent target of chromosomal mutation in human leukemia, is absolutely required for HSC specification in mammals;runx1 expression is conserved in ..
  25. MECHANISMS OF RADIORESISTANCE AND CELL CYCLE PROGRESSION
    Howard B Lieberman; Fiscal Year: 2013
    ..that damage DNA, or develop damage during normal metabolic processes, deleterious effects can ensue, including mutation, cancer or death...
  26. Prevention of Inherited Retinal Diseases by Therapeutic Rare Earth Nanoparticles
    JAMES FRANCIS MCGINNIS; Fiscal Year: 2010
    ..Irrespective of the primary mutation or cause, all of these diseases are thought to share a major common event...
  27. Cellular and Animal Models of FUS Mutations in ALS
    Eric J Huang; Fiscal Year: 2013
    ..Among the FUS mutations, the most common form in adult ALS patients is the R521C mutation. In addition, our recent study indicates that the P525L mutation in FUS leads to a more aggressive and rapidly ..
  28. Signaling by Cytoplasmic Tyrosine Kinases in Leukocytes
    Clifford A Lowell; Fiscal Year: 2013
    ..b>Mutation of the SHP-1 gene (Ptpn6) results in severely hyperactive lymphocytes, myeloid cells and platelets...
  29. CPG METHYLATION AND MUTATION
    Gerd P Pfeifer; Fiscal Year: 2013
    ..In parallel, we will study molecular pathways involving the Polycomb repression complex that might operate during tumor progression to promote hypermethylation of CpG islands in malignant tissue. ..
  30. Genetics of the Neuromuscular Junction: Mechanisms and Disease Models
    Robert W Burgess; Fiscal Year: 2013
    ..motor deficits (diagnosed as distal Spinal Muscular Atrophy type V, dSMAV), whereas others carrying the same mutation present with both motor and sensory deficits...
  31. Mechanisms of Neutralizing Antibody Resistance in Chronic HCV and HIV Infection
    JUSTIN RICHARD BAILEY; Fiscal Year: 2013
    ..of this K08 career development award are to to define shared patterns of hepatitis C virus (HCV) envelope mutation that mediate escape from autologous neutralizing antibody (nAb), to measure the fitness costs of those mutations, ..
  32. Regulation of K-Ras by a Farnesyl-electrostatic Switch
    MARK REID PHILIPS; Fiscal Year: 2013
    ..We will correlate susceptibility of human tumor cells lines with K-Ras mutation status and generate isogenic lines of human tumor cells with and without a phosphorylation site at position 181...
  33. Mechanisms of Stem Cell Self-Renewal and Aging
    PAUL CHRISTIAN SCHILLER; Fiscal Year: 2013
    ..The LMNA mutation C1824T activates a cryptic splice site in exon 11 leading to the production of the unprocessed farnesylated LMNA ..
  34. Phosphotyrosine signaling pathways controlling tracheal tube geometry
    KAI G ZINN; Fiscal Year: 2013
    ..We obtained an entry point into this problem when we discovered a unique tracheal phenotype caused by a double mutation eliminating both of the Type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D...
  35. Mouse models of genomic instability and birth defects
    CATHERINE ELIZABETH KEEGAN; Fiscal Year: 2013
    Adrenocortical dysplasia (acd) is a spontaneous autosomal recessive mouse mutation that exhibits a pleiotropic phenotype that includes embryonic and perinatal lethality...
  36. Characterization of epsilon-sarcoglycan interacting proteins in mouse brain
    Yuqing Li; Fiscal Year: 2012
    ..The results should help us to determine the function of ?-SG in vivo and how the mutation of Sgce causes M-D...
  37. Novel SCID rat models for human cell transplantation studies
    Joseph C Ruiz; Fiscal Year: 2010
    ..project will investigate the use of a novel rat strain carrying a transposon-mediated knockout (KO) insertional mutation within the adenosine deaminase (Ada) locus in the inbred Fischer line...
  38. Interaction between RNA interference and RNA editing pathways
    Kazuko Nishikura; Fiscal Year: 2013
    ..Furthermore, we have created an ADAR1-/- mutation in mice that causes widespread apoptosis and consequent embryonic lethal phenotypes...
  39. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..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...
  40. Identifying all Meckel-like ciliopathy genes by established total exome capture a
    Friedhelm Hildebrandt; Fiscal Year: 2010
    ..yields to many variants from normal reference sequence, which prohibits identification of the disease-causing mutation. Using this approach we already identified mutations in SDCCAG8, PRKACA and MAP2 as novel causes of Meckel-like ..
  41. Combined BAC Transgenic and Knock-Out Mouse Model of Lowe Syndrome Nephropathy
    Robert L Nussbaum; Fiscal Year: 2013
    ..Mice with a mutation in Inpp5b have only a mild phenotype but mutation of both Ocrl and Inpp5b causes early embryonic lethality, ..
  42. Growth Hormone Regulation of SH2B1
    Christin Carter-Su; Fiscal Year: 2013
    ..They are critical to normal human physiology, such that their impairment due to mutation contributes to the dramatic phenotype observed in human patients...
  43. Role of Potent Trophic Factors on Glia and Motor Neurons in ALS
    Brian K Kaspar; Fiscal Year: 2013
    ..Recent studies have surprisingly demonstrated that astrocytes and microglia expressing a mutation in the enzyme superoxide dismutase can exacerbate motor neuron death, supporting earlier studies that ALS is a ..
  44. Intermediary Metabolism, Histone Acetylation, and Transcriptional Regulation
    Ales Vancura; Fiscal Year: 2013
    ..via the glycolytic pathway, and subsequently histone acetylation, are significantly reduced in cells with mutation of phospholipase C (PLC1)...
  45. Regulation of Genomic and Epigenomic Stability at CpG Sites
    Alfonso Bellacosa; Fiscal Year: 2013
    ..by measuring: G:T and G:U mismatch repair in genetically defined cell lines (deficient in TDG, MED1 or both), mutation frequency and altered methylation of single- and MED1-TDG double-mutant mice...
  46. Development of a Porcine Model of Atherosclerosis
    Christopher Rogers; Fiscal Year: 2010
    ..Although the hypercholesterolemic pig is an attractive model, the mild nature of the mutation, the high variability of the disease and the limited access by other researchers prevents its wide use in the ..
  47. Pax8-PPARgamma regulation of transcription and metabolism in thyroid cancer
    RONALD JAY KOENIG; Fiscal Year: 2013
    ..The importance of PPFP functional domains on xenograft tumor formation and metastases will be assessed with DoxyPPFP cell lines expressing mutant PPFPs (for example, mutation of either the PAX8 or PPARg DNA binding domain).
  48. Roles of NF-kB/Rel in the pathogenesis of breast cancer
    Gail E Sonenshein; Fiscal Year: 2012
    ..Carcinogens induce overexpression or mutation in cancer-causing genes that signal via this family of factors, and the PI's group has identified new ..
  49. The function of ATM protein in the biology of the adult neuron CNS:
    Karl Herrup; Fiscal Year: 2013
    ..by applicant): Ataxia-telangiectasia (A-T) is a profoundly destructive childhood disorder resulting from mutation of a gene encoding a member of the PI3 kinase family...
  50. 14th International Workshop on Ataxia-Telangiectasia and ATM
    Richard A Gatti; Fiscal Year: 2010
    ..A-T has also become a model for the study of mutation-targeted drugs for correcting genetic diseases...
  51. Exon capture and large-scale sequencing for disease-cause identification, early d
    Friedhelm Hildebrandt; Fiscal Year: 2010
    ..In 30-80% of cases it yielded homozygous candidate regions, which contained the disease causing homozygous mutation in 93% of cases...
  52. Persisting Grand Mal and Myoclonic Seizures in JME including Veterans
    Antonio V Delgado-Escueta; Fiscal Year: 2013
    ..Specific Aim 1 involves human mutation analysis of JME genes and asks: Are mutations in Myoclonin1/EFHC1 population specific? (Aim 1a) Screen for new ..
  53. Misty: a model for central regulation of bone remodeling
    CLIFFORD JAMES ROSEN; Fiscal Year: 2013
    ..Misty has a 'loss of function'mutation in Dock7, a protein highly expressed in Schwann cells that affects cell migration...
  54. Molecular Pathogenesis of MDS and CMML
    Jaroslaw P Maciejewski; Fiscal Year: 2013
    ..By sequencing the c-Cbl gene, an E3 ubiquitin ligase in this chromosomal region, a mutation involving a critical part of this gene was identified...
  55. Dietary Risk for Colon Cancer in the Mouse
    Leonard H Augenlicht; Fiscal Year: 2013
    ..Aim 2 employs a model that more closely recapitulates human sporadic colon cancer in that conditional/inducible mutation of the Apc gene will be used to determine how the diets fed for 6 months prime the mucosa for development of ..
  56. Role of troponin T isoforms in nemaline myopathy
    Jian Ping Jin; Fiscal Year: 2012
    ..The ANM allele contains a nonsense mutation in the slow skeletal muscle troponin T (TnT) gene (TNNT1), which results in truncation of the TnT protein at ..
  57. Molecular Pathological Mechanism & Potential Therapeutics of Lafora Disease
    YAN NONE LIU; Fiscal Year: 2010
    ..Therefore, the aggregates and ER stress that are initiated by the mutation in EPM2A gene could be two major pathological causes for LD development...
  58. Effects of periodontitis on insulin target organs and glucose homeostasis
    Keiko Watanabe; Fiscal Year: 2013
    ..explored the role of TLR4 in mediating periodontitis-enhanced IR using mice with TLR4 loss-of-function (LOF) mutation and wild-type (WT) controls...
  59. Pathogenesis of Postoperative Cognitive Dysfunction
    Zhongcong Xie; Fiscal Year: 2013
    ..POCD pathogenesis by testing the hypothesis that: surgery-induced neuroinflammation will interact with the gene mutation- or aging-induced elevation of A[unreadable] levels, leading to impairment of learning/memory and attention/..
  60. AKAP Regulation of PKA Targeting in the Heart
    Meredith Bond; Fiscal Year: 2009
    ..phage display, by co- immunoprecipitation by the regulatory subunit RII of PKA;and disruption of RII binding by mutation of the RII binding site to an inactive prolinated derivative;we showed by quantitative PCR (qPCR) that Chd8 mRNA ..
  61. 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...
  62. NOX1 and NOX2 as Therapeutic Targets in Influenza
    JOHN DAVID LAMBETH; Fiscal Year: 2013
    Description (as provided by the applicant): Influenza virus shows high rates of mutation and recombination that soon renders immunization ineffective and requires yearly production of vaccines...
  63. Ionic currents in gastrointestinal smooth muscle
    Hamid I Akbarali; Fiscal Year: 2013
    ..Preliminary data show that mutation of the terminal tyrosine residue within the c-terminus of the Ca2+ channel prevents the docking of the src ..
  64. Testing the Therapeutic Potential of iPS Cells for Inherited Skin Diseases
    Jakub Tolar; Fiscal Year: 2013
    ..stability of iPSC-derived cells We have also designed a ZFN-mediated strategy to inactivate a 'hot spot mutation" responsible for ~70% of the EBS-DM cases...
  65. NEW GENE THERAPY FOR CONNECTIVE TISSUE DISEASES
    Eric Kmiec; Fiscal Year: 1999
    Many inherited connective tissue diseases result from a point mutation or frame-shift mutation...
  66. MOLECULAR ANALYSIS OF CHROMOSOME SEGREGATION IN YEAST
    Clarence Chan; Fiscal Year: 1999
    ..a clever screen to detect mutations which lead to increases in ploidy, the PI previously isolated a conditional mutation in the IPL1 gene which has significant sequence homology with a number of kinases implicated in chromosome ..
  67. CELLULAR AND MOLECULAR RESPONSE TO DNA REPAIR DEFICIENCY
    Renee Reijo Pera; Fiscal Year: 2000
    DESCRIPTION: This research team has recently created a mouse that is heterozygous for a null mutation in the DNA repair gene XRCC1 (X-ray repair cross-complementing)...
  68. Peripheral Biomarkers in Familial Alzheimer's Disease
    Paul Coleman; Fiscal Year: 2009
    ..The central hypothesis to be tested by the research proposed here is, then;that those persons with an FAD mutation but diagnosis of no AD represent "preclinical" AD and that they will present a gene expression profile that will ..
  69. Phase 2a Study of Ataluren in Hemophilia A and B (IND 104,321)
    JAY A BARTH; Fiscal Year: 2010
    ..activity, safety, and pharmacokinetic study of ataluren in patients with nonsense-mutation-mediated hemophilia A and B (HA/HB), rare and life-threatening genetic disorders...
  70. Immunoglobulin Somatic Mutation
    Ursula Storb; Fiscal Year: 2007
    ..will be isolated at various cell cycle stages and screened for molecular intermediates consistent with an ongoing mutation process...
  71. Hereditary Spastic Paraplegia due to SPG3A/atlastin mutation
    John Fink; Fiscal Year: 2009
    ..Although clinical variation sometimes correlates with discrete SPGSA/atlastin mutation, variation between subjects with the same mutation indicates the action of modifying factors...
  72. GENETICS OF ALCOHOLISM IN AMERICAN INDIANS
    Richard Deitrich; Fiscal Year: 1993
    ..Among Orientals a single gene mutation has been identified which decreases alcohol intake...
  73. CLONING OF THE Hol MUTATION
    Licia Selleri; Fiscal Year: 2009
    ..Overall, the Hol craniofacial mutation phenocopies the Tbx1 homozygous mutation in the mouse, which models DiGeorge Syndrome (DGS)...
  74. MUTATION IDENTIFICATION IN HERITABLE CHONDRODYSTROPHIES
    Deborah Redford Badwal; Fiscal Year: 1993
    The combination of genetic linkage, mutation localization and DNA sequencing have greatly increased our understanding of the molecular basis of heritable connective tissue disorders affecting type I collagen...
  75. Role of Parkin in Regulating Manganese Toxicity
    JEROME ALLAN ROTH; Fiscal Year: 2010
    ..This application will apply non-human modeling to examine a genetic mutation which may be responsible for increasing susceptibility to develop manganese (Mn) toxicity...
  76. mtDNA mutation/heteroplasmy: a sensitive functional biomarker of oxidative stress
    Bruce N Ames; Fiscal Year: 2010
    ..We propose that mutation is a disease-relevant target endpoint because of its known association with aging and causal relationship to ..
  77. Pre-BCR Function Selecting Novel B Cell Receptors in Chronic Lymphocytic Leukemia
    Kyoko Hayakawa; Fiscal Year: 2010
    ..In the past ten years it has become clear that CLL can be subdivided into two categories based on extent of mutation of the B cell antigen receptor (BCR): those with significant mutation (>2%) show slower progression and ..
  78. RISK OF CANCER IN A-T FAMILIES
    Robert Haile; Fiscal Year: 2003
    Our overall objective is to determine whether subjects who are heterozygotes for mutation in the gene presently identified as a cause of ataxia-telangiectasia (ATM) have a higher that expected risk of cancer, with a primary focus on ..
  79. Nuclear modifier genes for maternally inherited deafness
    Min Xin Guan; Fiscal Year: 2010
    ..Mitochondrial 12S rRNA A1555G mutation has been found in many families of various ethnic origins with variable penetrance and expressivity of ..