exons

Summary

Summary: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or structural RNA.

Top Publications

  1. pmc Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
    Mitchell Guttman
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 458:223-7. 2009
  2. pmc Alternative isoform regulation in human tissue transcriptomes
    Eric T Wang
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 456:470-6. 2008
  3. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
  4. ncbi Mapping and quantifying mammalian transcriptomes by RNA-Seq
    Ali Mortazavi
    Division of Biology, MC 156 29, California Institute of Technology, Pasadena, California 91125, USA
    Nat Methods 5:621-8. 2008
  5. pmc Detecting differential usage of exons from RNA-seq data
    Simon Anders
    European Molecular Biology Laboratory, 69111 Heidelberg, Germany
    Genome Res 22:2008-17. 2012
  6. ncbi RNA maps reveal new RNA classes and a possible function for pervasive transcription
    Philipp Kapranov
    Affymetrix Laboratory, Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA, 95051, USA
    Science 316:1484-8. 2007
  7. pmc RNA-Seq: a revolutionary tool for transcriptomics
    Zhong Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, Connecticut 06520, USA
    Nat Rev Genet 10:57-63. 2009
  8. pmc Analysis and design of RNA sequencing experiments for identifying isoform regulation
    Yarden Katz
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    Nat Methods 7:1009-15. 2010
  9. ncbi Listening to silence and understanding nonsense: exonic mutations that affect splicing
    Luca Cartegni
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 3:285-98. 2002
  10. pmc Conservation and divergence of methylation patterning in plants and animals
    Suhua Feng
    Howard Hughes Medical Institute, Department of Molecular, Cell and Developmental Biology, and Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 107:8689-94. 2010

Research Grants

Detail Information

Publications336 found, 100 shown here

  1. pmc Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
    Mitchell Guttman
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 458:223-7. 2009
    ..Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes...
  2. pmc Alternative isoform regulation in human tissue transcriptomes
    Eric T Wang
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 456:470-6. 2008
    ....
  3. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
    ..Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function...
  4. ncbi Mapping and quantifying mammalian transcriptomes by RNA-Seq
    Ali Mortazavi
    Division of Biology, MC 156 29, California Institute of Technology, Pasadena, California 91125, USA
    Nat Methods 5:621-8. 2008
    ..Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3' ..
  5. pmc Detecting differential usage of exons from RNA-seq data
    Simon Anders
    European Molecular Biology Laboratory, 69111 Heidelberg, Germany
    Genome Res 22:2008-17. 2012
    ..DEXSeq detects with high sensitivity genes, and in many cases exons, that are subject to differential exon usage...
  6. ncbi RNA maps reveal new RNA classes and a possible function for pervasive transcription
    Philipp Kapranov
    Affymetrix Laboratory, Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA, 95051, USA
    Science 316:1484-8. 2007
    ..These data support a highly interleaved organization of the human transcriptome...
  7. pmc RNA-Seq: a revolutionary tool for transcriptomics
    Zhong Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, Connecticut 06520, USA
    Nat Rev Genet 10:57-63. 2009
    ..This article describes the RNA-Seq approach, the challenges associated with its application, and the advances made so far in characterizing several eukaryote transcriptomes...
  8. pmc Analysis and design of RNA sequencing experiments for identifying isoform regulation
    Yarden Katz
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    Nat Methods 7:1009-15. 2010
    ..the mixture-of-isoforms (MISO) model, a statistical model that estimates expression of alternatively spliced exons and isoforms and assesses confidence in these estimates...
  9. ncbi Listening to silence and understanding nonsense: exonic mutations that affect splicing
    Luca Cartegni
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 3:285-98. 2002
    ..even translationally silent mutations can inactivate genes by inducing the splicing machinery to skip the mutant exons. Similarly, coding-region single-nucleotide polymorphisms might cause phenotypic variability by influencing ..
  10. pmc Conservation and divergence of methylation patterning in plants and animals
    Suhua Feng
    Howard Hughes Medical Institute, Department of Molecular, Cell and Developmental Biology, and Institute for Genomics and Proteomics, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 107:8689-94. 2010
    ..Gene body methylation is conserved with clear preference for exons in most organisms. Furthermore, genes appear to be the major target of methylation in Ciona and honey bee...
  11. pmc Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data
    Manhong Dai
    Molecular and Behavioural Neuroscience Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA
    Nucleic Acids Res 33:e175. 2005
    ..It will be beneficial to re-analyze existing GeneChip data with updated probe set definitions...
  12. pmc Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study
    Sebahattin Cirak
    Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK
    Lancet 378:595-605. 2011
    ..We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy...
  13. pmc Regulation of alternative splicing by histone modifications
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 327:996-1000. 2010
    ..Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery...
  14. pmc Relationship between nucleosome positioning and DNA methylation
    Ramakrishna K Chodavarapu
    Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA
    Nature 466:388-92. 2010
    ..Finally, as has been observed in animals, nucleosomes were highly enriched on exons, and preferentially positioned at intron-exon and exon-intron boundaries...
  15. pmc The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing
    Eugene V Makeyev
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Mol Cell 27:435-48. 2007
    ..Thus, miR-124 promotes NS development, at least in part by regulating an intricate network of NS-specific alternative splicing...
  16. ncbi Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17
    M Hutton
    Mayo Clinic Jacksonville, Florida 32224, USA
    Nature 393:702-5. 1998
    ..The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17...
  17. ncbi Systemic administration of PRO051 in Duchenne's muscular dystrophy
    Nathalie M Goemans
    Department of Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium
    N Engl J Med 364:1513-22. 2011
    ..The present phase 1-2a study aimed to assess the safety, pharmacokinetics, and molecular and clinical effects of systemically administered PRO051...
  18. pmc Differential chromatin marking of introns and expressed exons by H3K36me3
    Paulina Kolasinska-Zwierz
    The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
    Nat Genet 41:376-81. 2009
    ..We also observe a novel pattern: exons are preferentially marked with H3K36me3 relative to introns...
  19. ncbi Identification and characterization of a spinal muscular atrophy-determining gene
    S Lefebvre
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, Institut National de la Sante et de la Recherche Medicale, Institut Necker, Hopital des Enfants Malades, Paris, France
    Cell 80:155-65. 1995
    ..These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene...
  20. pmc Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing
    Andreas Gnirke
    Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nat Biotechnol 27:182-9. 2009
    ..We tested this method with 170-mer baits that target >15,000 coding exons (2.5 Mb) and four regions (1.7 Mb total) using Illumina sequencing as read-out...
  21. ncbi The sequence of the human genome
    J C Venter
    Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA
    Science 291:1304-51. 2001
    ..Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA...
  22. ncbi A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome
    Marc Sultan
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany
    Science 321:956-60. 2008
    ..Of these, 50% mapped to unique genomic locations, of which 80% corresponded to known exons. We found that 66% of the polyadenylated transcriptome mapped to known genes and 34% to nonannotated genomic ..
  23. ncbi Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
    Maria Eriksson
    Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    Nature 423:293-8. 2003
    ..The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing...
  24. ncbi Messenger-RNA-binding proteins and the messages they carry
    Gideon Dreyfuss
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    Nat Rev Mol Cell Biol 3:195-205. 2002
    ..These proteins communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation...
  25. 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...
  26. pmc Targeted capture and massively parallel sequencing of 12 human exomes
    Sarah B Ng
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Nature 461:272-6. 2009
    ..This strategy may be extendable to diseases with more complex genetics through larger sample sizes and appropriate weighting of non-synonymous variants by predicted functional impact...
  27. pmc Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping
    Yuanchao Xue
    Wuhan University, Hubei, China
    Mol Cell 36:996-1006. 2009
    ....
  28. ncbi CLIP identifies Nova-regulated RNA networks in the brain
    Jernej Ule
    Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    Science 302:1212-5. 2003
    ..Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA...
  29. pmc Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer
    Rong Hu
    Department of Urology, Oncology, and Pathology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Cancer Res 69:16-22. 2009
    ..variant transcripts lacking the reading frames for the ligand-binding domain due to splicing of "intronic" cryptic exons to the upstream exons encoding the AR DNA-binding domain...
  30. pmc HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
    Charles J David
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 463:364-8. 2010
    ..Our results thus define a pathway that regulates an alternative splicing event required for tumour cell proliferation...
  31. pmc Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs
    Hagen Tilgner
    Centre for Genomic Regulation and UPF, E 08003, Barcelona, Catalonia, Spain
    Genome Res 22:1616-25. 2012
    ..RNA-seq reads mapping to exon junctions and borders, to assess the degree of splicing completion around internal exons. We show that, as expected, splicing is almost fully completed in cytosolic polyA+ RNA...
  32. pmc Sex-specific and lineage-specific alternative splicing in primates
    Ran Blekhman
    Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA
    Genome Res 20:180-9. 2010
    ....
  33. pmc Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome
    Christian Gilissen
    Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Hum Genet 87:418-23. 2010
    ..WDR35 is homologous to TULP4 (from the Tubby superfamily) and has previously been characterized as an intraflagellar transport component, confirming that Sensenbrenner syndrome is a ciliary disorder...
  34. ncbi Genome-wide insertional mutagenesis of Arabidopsis thaliana
    Jose M Alonso
    Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Science 301:653-7. 2003
    ..Insertion mutations were identified in genes that are regulated in response to the plant hormone ethylene...
  35. pmc Statistical significance for genomewide studies
    John D Storey
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:9440-5. 2003
    ..Our approach avoids a flood of false positive results, while offering a more liberal criterion than what has been used in genome scans for linkage...
  36. pmc Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay
    Isao Kashima
    Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
    Genes Dev 20:355-67. 2006
    ..Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD...
  37. ncbi Alternative splicing and evolution: diversification, exon definition and function
    Hadas Keren
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
    Nat Rev Genet 11:345-55. 2010
    ....
  38. ncbi Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants
    Yingrui Li
    BGI Shenzhen, Shenzhen, China
    Nat Genet 42:969-72. 2010
    ..This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive...
  39. pmc Noisy splicing drives mRNA isoform diversity in human cells
    Joseph K Pickrell
    Department of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America
    PLoS Genet 6:e1001236. 2010
    ..We show that sequence motifs involved in the recognition of exons are enriched in the vicinity of unconserved splice sites...
  40. pmc RNA-seq: technical variability and sampling
    Lauren M McIntyre
    Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA
    BMC Genomics 12:293. 2011
    ..Alternative splicing of transcript isoforms and the identification of previously unknown exons are being reported...
  41. pmc ESEfinder: A web resource to identify exonic splicing enhancers
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Nucleic Acids Res 31:3568-71. 2003
    ..ESEs also appear to be especially important in exons that normally undergo alternative splicing...
  42. pmc HITS-CLIP yields genome-wide insights into brain alternative RNA processing
    Donny D Licatalosi
    Laboratory of Molecular Neuro Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 456:464-9. 2008
    ..HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo...
  43. pmc Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB
    Miriam Llorian
    Department of Biochemistry, University of Cambridge, Cambridge, UK
    Nat Struct Mol Biol 17:1114-23. 2010
    ..The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events...
  44. pmc Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome
    Alekos Athanasiadis
    Department of Biological Sciences, Lehigh University Bethlehem, Pennsylvania, USA
    PLoS Biol 2:e391. 2004
    ..to the posttranscriptional creation or elimination of splice signals affecting alternatively spliced Alu-derived exons. The analysis suggests that modification of repetitive elements is a predominant activity for RNA editing with ..
  45. ncbi Mutation of the PIK3CA gene in ovarian and breast cancer
    Ian G Campbell
    VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Cancer Res 64:7678-81. 2004
    ..We have screened a total of 284 primary human tumors for mutations in all coding exons of PIK3CA using a combination of single stranded conformational polymorphism and denaturing high-performance ..
  46. ncbi Local dystrophin restoration with antisense oligonucleotide PRO051
    Judith C van Deutekom
    Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 357:2677-86. 2007
    ..We explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease...
  47. ncbi Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses
    Tim F Oberlander
    Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
    Epigenetics 3:97-106. 2008
    ....
  48. pmc Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls
    Chaolin Zhang
    Laboratory of Molecular Neuro Oncology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 329:439-43. 2010
    ..Thus, we have developed a general approach to understanding mammalian RNA regulation at the systems level...
  49. ncbi Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9
    E Buratti
    International Center for Genetic Engineering and Biotechnology ICGEB 34012 Trieste, Italy
    J Biol Chem 276:36337-43. 2001
    ..In particular, the highly conserved Phe residues in the first RRM region play a key role in nucleic acid recognition...
  50. pmc Complement factor H polymorphism in age-related macular degeneration
    Robert J Klein
    Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 308:385-9. 2005
    ..This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies...
  51. ncbi Identification of FAP locus genes from chromosome 5q21
    K W Kinzler
    Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231
    Science 253:661-5. 1991
    ..Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia...
  52. pmc Muscleblind proteins regulate alternative splicing
    Thai H Ho
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    EMBO J 23:3103-12. 2004
    ..Alternative cTNT and IR exons are also regulated by CELF proteins, which were previously implicated in DM pathogenesis...
  53. ncbi Global analysis of nascent RNA reveals transcriptional pausing in terminal exons
    Fernando Carrillo Oesterreich
    Max Planck Institute of Molecular Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Mol Cell 40:571-81. 2010
    ..Indeed, splicing catalysis is expected to occur posttranscriptionally in yeast, where the shortness of terminal exons should leave insufficient time for splicing. Here, we isolate endogenous S...
  54. pmc A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters
    Serge Saxonov
    Biomedical Informatics Program, Stanford University, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 103:1412-7. 2006
    ....
  55. pmc PAL2NAL: robust conversion of protein sequence alignments into the corresponding codon alignments
    Mikita Suyama
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nucleic Acids Res 34:W609-12. 2006
    ..Another distinct feature is that the user can specify a subregion of the input alignment in order to specifically analyze functional domains or exons of interest. The PAL2NAL server is available at http://www.bork.embl.de/pal2nal.
  56. ncbi The PIK3CA gene is mutated with high frequency in human breast cancers
    Kurtis E Bachman
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Department of Oncology, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 3:772-5. 2004
    ..These results demonstrate that PIK3CA is the most mutated oncogene in breast cancer and support a role for PIK3CA in epithelial carcinogenesis...
  57. pmc ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing
    Claude C Warzecha
    Department of Medicine, Renal Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 33:591-601. 2009
    ..isoforms of Fibroblast Growth Factor Receptor 2 (FGFR2) is achieved through tight regulation of mutually exclusive exons IIIb and IIIc, respectively...
  58. pmc Identification of evolutionarily conserved exons as regulated targets for the splicing activator tra2β in development
    Sushma Grellscheid
    Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
    PLoS Genet 7:e1002390. 2011
    ..Using CLIP coupled to deep sequencing, we found that Tra2β binds a high frequency of exons and identified specific G/A rich motifs as frequent targets...
  59. ncbi Regulation of Fas alternative splicing by antagonistic effects of TIA-1 and PTB on exon definition
    Jose Maria Izquierdo
    Centre de Regulacio Genomica, Passeig Maritim 37 49, 08003 Barcelona, Spain
    Mol Cell 19:475-84. 2005
    ..We propose that TIA-1 and PTB regulate Fas splicing and possibly Fas-mediated apoptosis by targeting molecular events that lead to exon definition...
  60. pmc Role of RNA structure in regulating pre-mRNA splicing
    M Bryan Warf
    Institute of Molecular Biology, and Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA
    Trends Biochem Sci 35:169-78. 2010
    ..Recent reports have identified proteins and small molecules that can regulate splicing by modulating RNA structures, thereby expanding our knowledge of the mechanisms used to regulate splicing...
  61. ncbi Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1
    Marjolijn J L Ligtenberg
    Department of Human Genetics 849, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 41:112-7. 2009
    ..from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM...
  62. pmc Comprehensive analysis of CpG islands in human chromosomes 21 and 22
    Daiya Takai
    Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 99:3740-5. 2002
    ..This finding is compatible with the recent detection of 5-methylcytosine in Drosophila, and might suggest that S. cerevisiae has, or once had, CpG methylation...
  63. ncbi Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution
    Brian T Wilhelm
    Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK
    Nature 453:1239-43. 2008
    ..Splicing efficiency was largely coordinated with transcript levels, and increased transcription led to increased splicing in test genes. Hundreds of introns showed such regulated splicing during cellular proliferation or differentiation...
  64. pmc Contrasting chromatin organization of CpG islands and exons in the human genome
    Jung Kyoon Choi
    Department of Biology and Brain Engineering, KAIST, 335 Gwahak ro, Daejeon 305 701, Republic of Korea
    Genome Biol 11:R70. 2010
    ..Intragenic nucleosomes and their modifications have been recently associated with RNA splicing. Because the function of intragenic DNA methylation remains unclear, I explored the possibility of its involvement in splicing regulation...
  65. pmc Extensive, recent intron gains in Daphnia populations
    Wenli Li
    Biology Department, Indiana University, Bloomington, IN 47405, USA
    Science 326:1260-2. 2009
    ....
  66. ncbi The molecular basis of muscular dystrophy in the mdx mouse: a point mutation
    P Sicinski
    Medical Research Unit, MRC Centre, Cambridge, United Kingdom
    Science 244:1578-80. 1989
    ..Sequence analysis of the amplification products showed that the mdx mouse has a single base substitution within an exon, which causes premature termination of the polypeptide chain...
  67. pmc Rates of in situ transcription and splicing in large human genes
    Jarnail Singh
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Nat Struct Mol Biol 16:1128-33. 2009
    ..These results show that the expression of large genes is unexpectedly rapid and efficient...
  68. pmc Genome-wide analysis of alternative splicing in Caenorhabditis elegans
    Arun K Ramani
    Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Ontario M5S 3E1, Canada
    Genome Res 21:342-8. 2011
    ..elegans to date, and are therefore expected to facilitate focused, high resolution in vivo functional assays of AS function...
  69. pmc Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells
    I Shimomura
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA
    J Clin Invest 99:838-45. 1997
    ..The divergence results from the use of two transcription start sites that produce two separate 5' exons, each of which is spliced to a common exon 2...
  70. ncbi SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN
    Thanh T Le
    Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, Ohio State University, Columbus, OH 43210, USA
    Hum Mol Genet 14:845-57. 2005
    ..The increased survival of the SMNDelta7 SMA mice we report will facilitate testing of therapies and indicates the importance of considering co-complexes of SMN and SMNDelta7 when analyzing SMN function...
  71. ncbi Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells
    Matthew C Lorincz
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Nat Struct Mol Biol 11:1068-75. 2004
    ..As the methylated region adopts a closed chromatin structure in vivo, we propose that dense intragenic DNA methylation in mammalian cells initiates formation of a chromatin structure that reduces the efficiency of Pol II elongation...
  72. pmc Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk
    Christin E Burd
    The Curriculum in Toxicology, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
    PLoS Genet 6:e1001233. 2010
    ..at very low copy numbers in primary and cultured cells; however, only the expression of ANRIL isoforms containing exons proximal to the INK4/ARF locus correlated with the ASVD risk alleles...
  73. pmc Widespread establishment and regulatory impact of Alu exons in human genes
    Shihao Shen
    Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 108:2837-42. 2011
    The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements...
  74. pmc Biased chromatin signatures around polyadenylation sites and exons
    Noah Spies
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Mol Cell 36:245-54. 2009
    ..Conversely, exons were associated with distinct peaks in nucleosome density...
  75. ncbi Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications
    Takayuki Kosaka
    Departments of Thoracic Surgery and Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
    Cancer Res 64:8919-23. 2004
    ..To gain further insights in the role of EGFR in lung carcinogenesis, we sequenced exons 18-21 of the tyrosine kinase domain using total RNA extracted from unselected 277 patients with lung cancer who ..
  76. ncbi Distributions of exons and introns in the human genome
    Meena Kishore Sakharkar
    Nanyang Centre for Supercomputing and Visualisation, N3 2c 113b, 50 Nanyang Avenue, Nanyang Technological University, Singapore
    In Silico Biol 4:387-93. 2004
    ..The 26,564 annotated genes in the human genome (build October, 2003) contain 233,785 exons and 207,344 introns. On average, there are 8.8 exons and 7.8 introns per gene...
  77. ncbi A muscleblind knockout model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA
    Science 302:1978-80. 2003
    ..Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA...
  78. pmc Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome
    Yang Bian
    Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Hum Mol Genet 18:1229-37. 2009
    ..These observations open the door to the discovery of novel therapies based on PTB overexpression and to detecting possible untoward effects of the overexpression...
  79. ncbi Alternative splicing and disease
    Jamal Tazi
    University of Montpellier II, Institute of Molecular Genetics, Centre Nationale de Recherche Scientifique, 1919 Route de Mende, France
    Biochim Biophys Acta 1792:14-26. 2009
    ..Here, we discuss well-studied examples that show how a disturbance of this balance can cause human disease. The rapidly emerging knowledge of splicing regulation now allows the development of treatment options...
  80. ncbi Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D
    H Bolz
    Institut fur Humangenetik, Universitatsklinikum Hamburg Eppendorf, Hamburg, Germany
    Nat Genet 27:108-12. 2001
    ..In an accompanying paper, it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse...
  81. ncbi Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice
    L Mangiarini
    Division of Medical and Molecular Genetics, UMDS, Guy s Hospital, London, United Kingdom
    Cell 87:493-506. 1996
    ..This transgenic model will greatly assist in an eventual understanding of the molecular pathology of HD and may open the way to the testing of intervention strategies...
  82. ncbi Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans
    H Krude
    Department of Pediatrics, Charite, Campus Virchow, Humboldt University Berlin, Germany
    Nat Genet 19:155-7. 1998
    ..These findings represent the first examples of a genetic defect within the POMC gene and define a new monogenic endocrine disorder resulting in early-onset obesity, adrenal insufficiency and red hair pigmentation...
  83. pmc Analysis of alternative splicing associated with aging and neurodegeneration in the human brain
    James R Tollervey
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
    Genome Res 21:1572-82. 2011
    ..In conclusion, the alternative splicing changes identified in this study provide a new link between aging and neurodegeneration...
  84. pmc Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer
    Christine M Misquitta-Ali
    Banting and Best Department of Medical Research, University of Toronto, Donnelly Centre, 160 College Street, Toronto, Ontario, Canada M5S 3E1
    Mol Cell Biol 31:138-50. 2011
    ..Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients...
  85. ncbi Cotranscriptional exon skipping in the genotoxic stress response
    Martin Dutertre
    Institut National de Santé et de Recherche Médicale U590, Centre Leon Berard, Lyon, France
    Nat Struct Mol Biol 17:1358-66. 2010
    ..This results in the cotranscriptional skipping of several exons of the MDM2 gene, which encodes the main p53 ubiquitin ligase...
  86. pmc Nucleosomes are well positioned in exons and carry characteristic histone modifications
    Robin Andersson
    The Linnaeus Centre for Bioinformatics, Uppsala University, Sweden
    Genome Res 19:1732-41. 2009
    ..Using public data, we here show that there is a higher nucleosome-positioning signal in internal human exons and that this positioning is independent of expression...
  87. ncbi Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion
    J T den Dunnen
    MGC Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands corrected
    Hum Mutat 15:7-12. 2000
    ..In this article, suggestions are presented for reporting just such complex mutations...
  88. pmc The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism
    Cynthia V Clower
    Division of Signal Transduction, Department of Systems Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:1894-9. 2010
    ..isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons. We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues, tumor cell lines, and during ..
  89. pmc The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes
    Ian C G Weaver
    Douglas Hospital Research Center, Montreal, Quebec, Canada H4H 1R3
    J Neurosci 27:1756-68. 2007
    ..The data are consistent with the hypothesis that NGFI-A participates in epigenetic programming of GR expression...
  90. ncbi The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C
    Shivendra Kishore
    Institut fur Biochemie, Emil Fischer Zentrum, Friedrich Alexander Universitat Erlangen Nurnberg, Fahrstrasse 17, 91054 Erlangen, Germany
    Science 311:230-2. 2006
    ..Our results show that a snoRNA regulates the processing of an mRNA expressed from a gene located on a different chromosome, and the results indicate that a defect in pre-mRNA processing contributes to the Prader-Willi syndrome...
  91. ncbi The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes
    Ben Woodman
    Department of Medical and Molecular Genetics, King s College London School of Medicine, London, UK
    Brain Res Bull 72:83-97. 2007
    ..This supports the continued use of the more high-throughput fragment models to identify mechanisms of pathogenesis and for preclinical screening...
  92. ncbi The grapevine genome sequence suggests ancestral hexaploidization in major angiosperm phyla
    Olivier Jaillon
    Genoscope CEA and UMR 8030 CNRS Genoscope Université d Evry, 2 rue Gaston Cremieux, BP5706, 91057 Evry, France
    Nature 449:463-7. 2007
    ..Furthermore, we explain the chronology of previously described whole-genome duplication events in the evolution of flowering plants...
  93. ncbi Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
    T Kitada
    Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    Nature 392:605-8. 1998
    ..The gene spans more than 500 kilobases and has 12 exons, five of which (exons 3-7) are deleted in the patient...
  94. pmc Transcribed dark matter: meaning or myth?
    Chris P Ponting
    MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK
    Hum Mol Genet 19:R162-8. 2010
    ..greatly improved annotations of protein-coding genes, but have also identified transcription outside of annotated exons. One resultant issue that has aroused dispute is the balance of transcription of known exons against transcription ..
  95. pmc Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta
    Amanda C Filiberto
    Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA
    Epigenetics 6:566-72. 2011
    ..Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function...
  96. pmc Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors
    Dawid G Nowak
    Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
    J Cell Sci 121:3487-95. 2008
    ....
  97. ncbi Splicing in disease: disruption of the splicing code and the decoding machinery
    Guey Shin Wang
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Rev Genet 8:749-61. 2007
    ..An unexpectedly large fraction of exonic mutations exhibit a primary pathogenic effect on splicing. Furthermore, normal genetic variation significantly contributes to disease severity and susceptibility by affecting splicing efficiency...
  98. ncbi Ultraconserved elements in the human genome
    Gill Bejerano
    Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    Science 304:1321-5. 2004
    ..These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and ..
  99. pmc Detection of single nucleotide variations in expressed exons of the human genome using RNA-Seq
    Iouri Chepelev
    Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA
    Nucleic Acids Res 37:e106. 2009
    ..single nucleotide variations (SNVs) are found in protein-coding regions, we propose to identify SNVs in expressed exons of the human genome using the recently developed RNA-Seq technique...
  100. ncbi A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
    Chloe James
    INSERM U362, Institut Gustave Roussy, Paris XI University, PR1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France
    Nature 434:1144-8. 2005
    ..As this mutation is also found in other myeloproliferative disorders, this unique mutation will permit a new molecular classification of these disorders and novel therapeutical approaches...

Research Grants67

  1. Infant Screening and Diagnosis of Duchenne Muscular Dys*
    Paul Fernhoff; Fiscal Year: 2007
    ..multiplex ligation-dependent probe amplification (MLPA) techniques to detect deletions and duplications in all 79 exons of the dystrophin gene...
  2. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..It involves precise excision of introns and joining of exons from primary transcripts in the nucleus to generate mature mRNA, the template for protein synthesis in the ..
  3. Expression of sFlt1 and its function in the glomerular endothelium
    Christie P Thomas; Fiscal Year: 2013
    ..of FLT1 coordinately regulating the transcription of Flt1 and sFlt1 and within intron 13 of FLT1 and neighboring exons reciprocally regulating Flt1 and sFlt1...
  4. Exome re-sequencing candidate loci for familial essential tremor
    Barry E Kosofsky; Fiscal Year: 2012
    ..6 Mb ETM2 (48,054 baits) and the 14.4 Mb ETM3 (30,796 baits) loci to include all regulatory regions, exons, splice sites, enhancer, and conserved intergenic regions...
  5. Cell signaling as a leukemia biomarker
    JAMES WILLIAM JACOBBERGER; Fiscal Year: 2013
    ..that signaling can be classified by patterns and determine any age or gender effects;3) to sequence 182 gene exons that may should impact on the signaling patterns for 10 MDS and 10 AML patients to demonstrate the feasibility of ..
  6. Non-coding RNA engineers antibody diversity
    Uttiya Basu; Fiscal Year: 2011
    ..reaction that replaces an Ig heavy chain constant region gene (CH) from C[unreadable] with other downstream CH exons so that secondary isotypes (IgG, IgA etc) with different effector functions are generated...
  7. Signaling Mechanisms in Alcohol Drinking Behaviors
    Subhash C Pandey; Fiscal Year: 2013
    ..It is also unknown how the expression of Arc and various exons of BDNF and its receptor, tyrosine kinase B (trkB)-linked signaling [cAMP responsive-element binding protein (CREB)..
  8. Neuropilin and semaphorin, anti-angiogenesis activities and mechanisms
    Michael Klagsbrun; Fiscal Year: 2009
    ..NRPs enhance the angiogenic activity of VEGF. A goal is to block VEGF-NRP interactions. VEGF, via its exons 7 and 8 (ex7/8), binds to the NRP B domain...
  9. Intravenous Protein Therapy for Myotonic Dystrophy Type 1
    Richard Weisbart; Fiscal Year: 2010
    ..DMPK mRNA avidly binds, sequesters and inactivates the MBNL1 protein, an mRNA splicing factor that removes fetal exons from mRNA templates (9- 13)...
  10. The Role of RNA Splicing Factors in Retinal Degeneration
    Michael Farkas; Fiscal Year: 2012
    ..where the spliceosome processes pre-mRNA transcripts by removing introns (non-coding regions) and splicing the exons (coding regions) together to form a mature mRNA transcript...
  11. Human Papillomavirus Association with Subsets of Colorectal Cancer
    Polly A Newcomb; Fiscal Year: 2010
    ..In addition, we will conduct DNA sequencing of tumor DNA to detect p53 mutations in exons 5-9 of the TP53 gene, where >90% of p53 mutations in cancerous cells occur...
  12. Nuclear Function of Abl in DNA Damage Response
    Jean Y J Wang; Fiscal Year: 2012
    ..approximately twenty thousand genes but encodes many more proteins through the alternative usage of variable exons. Alternative splicing has been shown to generate pro-death and anti-death protein isoforms from a single gene, ..
  13. Alternative Splicing of the Insulin Receptor Gene
    NICHOLAS J WEBSTER; Fiscal Year: 2013
    ..rise to multiple mRNAs resulting from differential promoters, termination sequences, or the use of alternative exons. Although often depicted as sequential steps, transcription and splicing are now thought to occur simultaneously, ..
  14. Genetic hearing screening for newborns
    Xi Lin; Fiscal Year: 2009
    ..This STTR project will test and validate the core technology for a low-cost approach to efficiently capture exons of deafness genes and its suitability for coupling with the massively-parallel sequencing system for the detection ..
  15. Characterization of Diet1, a hypercholesterolemia resistance gene
    Karen Reue; Fiscal Year: 2013
    ..We will resequence the DIET1 coding exons from individuals with extreme high and low bile acid and LDL-C levels in a population-based sample of 8000 ..
  16. Role of the Giant Protein Titin in Skeletal Muscle Structure and Function
    Henk L Granzier; Fiscal Year: 2013
    ..expressed in different muscle types, we developed a titin exon microarray which contains all of titin's exons found in a range of species (363 exons in human)...
  17. Role of ncRNA Surveillance Complex "RNA Exosome" in Class Switch Recombination an
    Uttiya Basu; Fiscal Year: 2013
    ..reaction that replaces an Ig heavy chain constant region gene (CH) from C[unreadable] with other downstream CH exons so that secondary isotypes (IgG, IgA etc) with different effector functions are generated...
  18. Genone-wide Discovery of Molecular Alterations in Head and Neck Cancer
    Victor E Velculescu; Fiscal Year: 2010
    ..of large scale tumor sequencing, providing highly sensitive mutational analysis of >95% of bases of ~200,000 exons from over 20,000 coding genes...
  19. The Role of Caspase 9b Expression in NSCLC Survival/Chemotherapeutic Sensitivity
    Charles E Chalfant; Fiscal Year: 2013
    ..of caspase 9b is regulated by alternative splicing via the inclusion or exclusion of a four exon cassette (exons 3, 4, 5, and 6)...
  20. Treatment for Dysmyelination in PMD and SPG2
    Pamela E Knapp; Fiscal Year: 2013
    ..The most severe forms of PMD are associated with missense mutations in introns or exons of the PLP1 gene. Interestingly, complete gene deletion results in a milder neurologic impairment...
  21. Molecular Basis of Autosomal Dominant Hypercholesterolemia in a Multiethnic Cohor
    Zahid Ahmad; Fiscal Year: 2013
    ..DNA will be screened with standard sequencing techniques for mutations in the exons and consensus splice sites of LDLR, APOB and PCSK9 or by linkage analysis using informative markers at these loci...
  22. Regulation of caspase 9 RNA splicing in NSCLC cancer
    Charles E Chalfant; Fiscal Year: 2013
    ..of caspase 9 is regulated by alternative splicing via the inclusion or exclusion of a four exon cassette (exons 3, 4, 5, and 6)...
  23. The Genetics of Polycystic Ovary Syndrom
    Corrine K Welt; Fiscal Year: 2013
    ..In addition, the exons and promoter regions of genes in linkage disequilibrium with the associated variant will be sequenced in large ..
  24. EPITHELIAL OXALATE AND CITRATE TRANSPORT
    DAVID BRUCE MOUNT; Fiscal Year: 2011
    ..To clarify the role of Slc26a6 in the proximal tubule we will generate mice in Aim 2 with loxP sites flanking exons 5-7 of the Slc26a6 gene ("floxed mice"), for cell type-specific deletion of these exons...
  25. POSTTRANSCRIPTIONAL REGULATION OF ANGIOTENSIN RECEPTORS
    KATHRYN L SANDBERG; Fiscal Year: 2011
    ..These transcripts are comprised of exons 1 and 3 (E1,3) and exons 1, 2 and 3 (E1,2,3)...
  26. Mechanisms for the Transition to Castrate Resistant Prostate Cancer
    Stephen R Plymate; Fiscal Year: 2013
    ..The specific variants we describe in the Work Accomplished have deletions of exons 5, 6, and 7 (AR del 5, 6, 7) or exons 5 and 6 (AR del 5, 6)...
  27. Polymorphism affecting water balance
    David M Cohen; Fiscal Year: 2013
    ..Although we strongly suspect that this is the case, based upon our sequencing of all coding exons and splice junctions in this block, a robust conclusion requires phasing the entire haplotype block...
  28. Regulation of SMAD4 and BMPR1A Expression in Juvenile Polyposis
    James R Howe; Fiscal Year: 2010
    ..Another JP patient has been found with a deletion of the putative promoter and first 2 non-coding exons of SMAD4, lending further support to this approach...
  29. Alternate pore isoforms of a mechanotransducing ion channel
    Maurice J Kernan; Fiscal Year: 2013
    ..at single-neuron resolution by transgenic "splice-reporter" genomic constructs, fluorescently tagged in alternate exons. The results will give insights into the structural determinants of mechanotransducer channel activation and ..
  30. A Haplotype Map for Multiple Sclerosis
    Stephen L Hauser; Fiscal Year: 2013
    ..In Specific Aim 3 we intend to generate high-coverage sequence information for the regulatory regions, exons and flanking regions of genes with unequivocal evidence of association for the discovery of rare variants ..
  31. Regulation of CD45 alternative splicing by HNRPLL
    Anjana Rao; Fiscal Year: 2013
    ..The CD45 gene consists of ~33 exons, of which exons 4, 5 and 6, encoding regions A, B and C of the extracellular domain respectively, can be variably ..
  32. HLA and schizophrenia: a high-throughput sequencing study
    DOUGLAS FREDERICK LEVINSON; Fiscal Year: 2013
    ..The entire targeted block of almost all exons and introns in 11 HLA genes in 8 loci (A, B, C, DRB1/3/4/5, DQA1, DQB1, DPA1, DPB1) will be amplified by long-..
  33. Spliceosome Mechanism Dissected at the Single Molecule Level
    Nils G Walter; Fiscal Year: 2013
    ..a multi-megadalton RNA-protein complex that catalyzes in all eukaryotes the removal of introns and the ligation of exons during splicing of pre mRNAs...
  34. MECHANISMS OF ENHANCER DEPENDENT SPLICE SITE ACTIVATION
    Klemens J Hertel; Fiscal Year: 2013
    ..activities of splicing regulators, and the discovery that the retention of spliceosomal components along ligated exons ensures efficient processing...
  35. GENETICS OF HYPERTENSION
    Ashok Kumar; Fiscal Year: 2013
    ..situation, we have re-combineered 180 Kb long BAC DNA (containing 116 Kb of the 5'-flanking region, all five exons and four introns, and 54 Kb of the 3'-UTR of the hAGT gene) and produced double transgenic mice containing ..
  36. Identification of Enhancers of Therapeutic Exon Skipping for DMD
    MELISSA JAN SPENCER; Fiscal Year: 2010
    ..Most of the mutations in DMD result from DNA deletions between exons 44-55...
  37. Identification and Classification of Epigenetic Changes in Head and Neck Cancer
    Thomas J Belbin; Fiscal Year: 2010
    ..DNA methylation of so called "CpG islands", CpG-rich sequences frequently associated with promoters or first exons, is associated with the inappropriate transcriptional silencing of critical genes...
  38. Discovery of Biomakers in Human Mitochondrial Disorders
    RONALD WAYNE DAVIS; Fiscal Year: 2011
    ..DNA sequence capture technologies and next-generation sequencing platforms for the targeted resequencing of human exons at high accuracy and completeness...
  39. Isolation of a cervical cancer tumor suppressor gene
    Eri S Srivatsan; Fiscal Year: 2012
    ..Examination of the three exons of cystatin E/M in 19 primary tumors and 21 normal tissues revealed homozygous deletion of exon 1 in one tumor...
  40. Large-Scale Discovery of Functional Genetic Variation in Rhesus Macaques
    JEFFREY A ROGERS; Fiscal Year: 2011
    ..To accomplish this, we will sequence the exome (all functional gene exons) from 96 unrelated rhesus macaques, both Indian-origin and Chinese-origin animals...
  41. The Lymphangioleiomyomatosis (LAM)Genome Atlas
    DAVID J contact KWIATKOWSKI; Fiscal Year: 2010
    ..Third, we will directly sequence all exons of 2,000 tumor-associated genes to comprehensively screen for other mutations...
  42. Neuronal-Specific Splicing of CaV1.2 L-type Calcium Channels
    Kristin Webster; Fiscal Year: 2013
    ..The N- terminus of CaV1.2 is encoded by alternative first exons;exon 1a (e1a) is the cardiac isoform and exon1b (e1b) has a broad expression pattern and is the only isoform ..
  43. Association of TFPI with antemortem dementia and postmortem micro brain infarcts
    SUSAN ANTONE MARONEY; Fiscal Year: 2013
    ..In Aim1 we will sequence the exons and 5'promoter region of the TFPI gene in all individuals to identify any polymorphisms and correlate the ..
  44. Physiologic role of the gamma epithelial sodium channel subunit in the kidney
    Donald E Kohan; Fiscal Year: 2010
    ..either in principal cells of the collecting duct or in the entire nephron;and 2) a mouse containing loxP-flanked exons critical to ? ENaC function. Breeding of these animals will result in distal nephron-knockout of ? ENaC...
  45. Stem cell derived neurons and inherited epilepsy
    Miriam H Meisler; Fiscal Year: 2010
    ..We will also investigate neuronal-specific splicing patterns of developmentally regulated alternative exons. We will study neurons carrying three classes of SCN1A mutations: splice site mutations, protein truncation ..
  46. Toward a comprehensive functional annotation of the human genome
    Richard M Myers; Fiscal Year: 2013
    ..This means discovering and mapping all parts of all genes, including exons, introns, promoters and cis-regulatory sequences, in previous phases of the ENCODE Project, the applicants of this ..
  47. Risk for in vivo mutagenesis of the P53 gene by nucleoside analog antiviral drug
    Vernon E Walker; Fiscal Year: 2011
    ..using psoralen-clamped primers, will be used to define the frequency and nature of mutations in p53 Exons 5-9 of cord blood lymphocytes from infants exposed in utero to AZT compared with those born to healthy uninfected ..
  48. BAYESIAN APPROACHES TO MODEL SELECTION FOR SURVIVAL DATA
    Joseph G Ibrahim; Fiscal Year: 2013
    ..mRNA greatly expands the functional repertoire of many genes in the mammalian genome by including or excluding the exons making up the genetic coding sequence...
  49. Genome-Wide Targeted Gene Resequencing in Glaucoma
    THERESA GAASTERLAND; Fiscal Year: 2010
    ..We will use a novel but proven sequencing strategy to identify coding variants in which all exons with some flanking intron are sequenced, approximately 30 million bases per patient, at 25- times coverage...
  50. Structural and Signaling Roles for Cardiac Ankyrin-B
    SHANE CUNHA; Fiscal Year: 2013
    ..Our recent findings demonstrate that ANK2, which encodes ankyrin-B, is comprised of 53 exons that are alternatively spliced to yield a diverse population of ankyrin-B polypeptides...
  51. Global Annotation of Regulatory Elements in the Human Genome
    Richard M Myers; Fiscal Year: 2011
    ..annotation of the human genome by delineating the DNA sequence features that comprise all genes, including exons, introns, promoters and cis-regulatory sequences...
  52. Next-Generation Medical Resequencing of Gout Disease Genes in the ARIC Cohort
    James E Hixson; Fiscal Year: 2010
    ..We have selected 11 genes from CHARGE GWAS results for resequencing of functional regions (promoters, exons, conserved regions) in gout cases and controls (total n=1,199) from the "Atherosclerosis Risk in Communities (ARIC)..
  53. Functional and Phenotypic Characterization of a New FSGS Gene
    RASHEED ADEBAYO GBADEGESIN; Fiscal Year: 2013
    ..3) To analyze mutations of the ANLN gene in a cohort of patients with FSGS. We will sequence the exons of ANLN in our cohort of FSGS patients and compare the disease phenotype in subjects with and without mutations...
  54. De Novo Methyltransferase Function in Chromatin and Cancer
    Keith D Robertson; Fiscal Year: 2013
    ..whole genome mapping of DNMT binding sites from our laboratory and the marked enrichment of methylation in exons, pinpoint important functions for DNA methylation and DNMTs in intragenic regions...
  55. Molecular Regulation of Cardiac KATP Channels in Ischemia
    Jonathan C Makielski; Fiscal Year: 2013
    ..A transgenic mouse model disrupting exons 12-16 (SUR2ex12-16) was constitutively protected from myocardial ischemia;it lacked long form SUR2 but retained ..
  56. Large-Scale Discovery of Functional Genetic Variation in Rhesus Macaques
    JEFFREY A ROGERS; Fiscal Year: 2013
    ..To accomplish this, we will sequence the exome (all functional gene exons) from 96 unrelated rhesus macaques, both Indian-origin and Chinese-origin animals...
  57. Exome Sequencing in Familial Cardiovascular Malformations
    KIM LEWIS MCBRIDE; Fiscal Year: 2012
    ..hypothesis will be tested by pursuing a single specific aim to use genome partitioning capture technology for the exons of all known human genes followed by massively parallel sequencing of the captured targets...
  58. Transcriptional elongation and splicing in human genes in situ
    Richard A Padgett; Fiscal Year: 2013
    ..For RNA splicing, very large introns present the problem of identifying the correct splice sites and exons in spite of a background of similar "decoy" sequences present within the introns...
  59. Comprehensive SNP Discovery in SLC2A9. A Candidate Gene for Uric Acid Nephropathy
    Venkata Saroja Voruganti; Fiscal Year: 2013
    ..which are associated with SUA and renal phenotypes in Mexican Americans 2) to resequence SLC2A9 gene (all exons, conserved introns and regulatory regions) for SNP/polymorphism discovery in 1122 founders in American Indians of ..
  60. TNFAIP3 (A20) and Susceptibility to Systemic Lupus Erythematosus
    Patrick M Gaffney; Fiscal Year: 2012
    ..In parallel, we will deeply resequence the region, focusing first on promoter, exons and UTR regions using conventional sequencing...
  61. Gene Regulatory Networks in Development and Physiology
    ALBERTHA JOHANNA WALHOUT; Fiscal Year: 2013
    ..g. promoters, exons, introns and enhancers) to differential gene expression in the digestive tract? We, and others, have generated ..
  62. Developing in vivo and in vitro Models for ALS Caused by Mutant FUS
    Xugang Xia; Fiscal Year: 2011
    ..FUS is a highly conserved ribonucleoprotein encoded by the FUS gene of 15 exons. While the physiological functions of FUS are largely unknown, mutation in FUS is definitely linked to ALS...
  63. TYPE III COLLAGEN GENE EXPRESSION IN CARTILAGE
    SHERRILL ADAMS; Fiscal Year: 1993
    ..The 3' half of this unique RNA is similar or identical to the authentic type III collagen mRNA. However, exons 1 and 2, as well as additional exons, appear to be missing from the 5' portion of the RNA...
  64. DNA Repair Defects in IgA Deficiency
    REUBEN HARRIS; Fiscal Year: 2009
    ..CSR) and it occurs between two so-called switch region sequences that reside upstream of the respective exons that encode the constant region of the antibody heavy chain...
  65. Comprehensive Mutational Analysis of the Cancer Genome
    Dennis Ballinger; Fiscal Year: 2004
    ..utility of this approach, we propose in this Phase I application to analyze at single base resolution all coding exons from chromosomes 1p, 6, 15, and 18 (approximately 16% of the genome), in each of 12 CRC genomes...
  66. Mechanisms Regulating Alternative pre-mRNA Splicing
    James Patton; Fiscal Year: 2005
    ..is remarkably efficient and rapid, an amazing feat considering that the signals that delineate introns from exons are not conserved in higher eukaryotes...
  67. Analyses of a Non tumorigenic Teratocarcinoma Cell Line
    Paulette McCormick; Fiscal Year: 2005
    ..The predominant transcript, -2.3kb, contains two exons, the second of which is disrupted by the insertion...