trinucleotide repeats

Summary

Summary: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.

Top Publications

  1. pmc Microsatellites in different eukaryotic genomes: survey and analysis
    G Toth
    Department of Genetics, Eotvos Lorand University, Budapest, Hungary
    Genome Res 10:967-81. 2000
  2. pmc Computational and experimental analysis of microsatellites in rice (Oryza sativa L.): frequency, length variation, transposon associations, and genetic marker potential
    S Temnykh
    Department of Plant Breeding, USDA-ARS Center for Agricultural Bioinformatics, Cornell University, Ithaca, New York 14853-1901, USA
    Genome Res 11:1441-52. 2001
  3. pmc Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy
    J W Miller
    Department of Molecular Genetics and Microbiology, Centers for Gene Therapy and Mammalian Genetics, University of Florida College of Medicine, Gainesville, FL 32610, USA
    EMBO J 19:4439-48. 2000
  4. ncbi Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion
    V Campuzano
    Department de Genetica, University of Valencia, Spain
    Science 271:1423-7. 1996
  5. ncbi Repeat instability as the basis for human diseases and as a potential target for therapy
    Arturo López Castel
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15 312, TMDT Toronto, Ontario, Canada, M5G 1L7
    Nat Rev Mol Cell Biol 11:165-70. 2010
  6. pmc Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae
    Wei Tang
    Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America
    PLoS Genet 7:e1001270. 2011
  7. pmc Crystal structures of CGG RNA repeats with implications for fragile X-associated tremor ataxia syndrome
    Agnieszka Kiliszek
    Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    Nucleic Acids Res 39:7308-15. 2011
  8. pmc Mechanisms of trinucleotide repeat instability during human development
    Cynthia T McMurray
    Lawrence Berkeley National Laboratory, Life Sciences Division, 1 Cyclotron Rd, 83R0101, Berkeley, California 94720, USA
    Nat Rev Genet 11:786-99. 2010
  9. ncbi Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2
    A Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Hum Mol Genet 10:2165-70. 2001
  10. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001

Detail Information

Publications262 found, 100 shown here

  1. pmc Microsatellites in different eukaryotic genomes: survey and analysis
    G Toth
    Department of Genetics, Eotvos Lorand University, Budapest, Hungary
    Genome Res 10:967-81. 2000
    ..We observed striking relative abundance of (CCG)(n)*(CGG)(n) trinucleotide repeats in intergenic regions of all vertebrates, in contrast to the almost complete lack of this motif from ..
  2. pmc Computational and experimental analysis of microsatellites in rice (Oryza sativa L.): frequency, length variation, transposon associations, and genetic marker potential
    S Temnykh
    Department of Plant Breeding, USDA-ARS Center for Agricultural Bioinformatics, Cornell University, Ithaca, New York 14853-1901, USA
    Genome Res 11:1441-52. 2001
    ..7 kb in BAC ends and every 1.9 kb in fully sequenced BAC and PAC clones. GC-rich trinucleotide repeats (TNRs) were most abundant in protein-coding portions of ESTs and in fully sequenced BACs and PACs, whereas ..
  3. pmc Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy
    J W Miller
    Department of Molecular Genetics and Microbiology, Centers for Gene Therapy and Mammalian Genetics, University of Florida College of Medicine, Gainesville, FL 32610, USA
    EMBO J 19:4439-48. 2000
    ..We propose that DM1 disease is caused by aberrant recruitment of the EXP proteins to the DMPK transcript (CUG)(n) expansion...
  4. ncbi Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion
    V Campuzano
    Department de Genetica, University of Valencia, Spain
    Science 271:1423-7. 1996
    ..A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron...
  5. ncbi Repeat instability as the basis for human diseases and as a potential target for therapy
    Arturo López Castel
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15 312, TMDT Toronto, Ontario, Canada, M5G 1L7
    Nat Rev Mol Cell Biol 11:165-70. 2010
    ....
  6. pmc Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae
    Wei Tang
    Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America
    PLoS Genet 7:e1001270. 2011
    ..These findings indicate that (GAA)(n)•(TTC)(n) tracts can be a potent source of loss of heterozygosity in yeast...
  7. pmc Crystal structures of CGG RNA repeats with implications for fragile X-associated tremor ataxia syndrome
    Agnieszka Kiliszek
    Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    Nucleic Acids Res 39:7308-15. 2011
    ..CGG helical structures appear relatively stable compared with CAG and CUG tracts. This could be an important factor in the RNA's ligand binding affinity and specificity...
  8. pmc Mechanisms of trinucleotide repeat instability during human development
    Cynthia T McMurray
    Lawrence Berkeley National Laboratory, Life Sciences Division, 1 Cyclotron Rd, 83R0101, Berkeley, California 94720, USA
    Nat Rev Genet 11:786-99. 2010
    ..We need now to connect the dots among human genetics, pathway biochemistry and the appropriate model systems to understand the mechanism of expansion as it occurs in human disease...
  9. ncbi Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2
    A Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Hum Mol Genet 10:2165-70. 2001
    ..These results support the idea that nuclear accumulation of mutant RNA is pathogenic in DM1, suggest that a similar disease process occurs in DM2, and point to a role for muscleblind in the pathogenesis of both disorders...
  10. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
    ..These results support a model in which increased expression of a splicing regulator contributes to insulin resistance in DM1 by affecting IR alternative splicing...
  11. ncbi Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum
    Vanessa C Wheeler
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Hum Mol Genet 12:273-81. 2003
    ..Therefore Msh2, as a striking modifier of early disease onset in a precise genetic HD mouse model, provides a novel target for the development of pharmacological agents that aim to slow pathogenesis in man...
  12. pmc Atomic resolution structure of CAG RNA repeats: structural insights and implications for the trinucleotide repeat expansion diseases
    Agnieszka Kiliszek
    Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    Nucleic Acids Res 38:8370-6. 2010
    ..The CAG repeats and the previously examined CUG structures share a similar pattern of electrostatic charge distribution in the minor groove, which could explain their affinity for the pathogenesis-related MBNL1 protein...
  13. pmc Isolated short CTG/CAG DNA slip-outs are repaired efficiently by hMutSbeta, but clustered slip-outs are poorly repaired
    Gagan B Panigrahi
    Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada M5G 1L7
    Proc Natl Acad Sci U S A 107:12593-8. 2010
    Expansions of CTG/CAG trinucleotide repeats, thought to involve slipped DNAs at the repeats, cause numerous diseases including myotonic dystrophy and Huntington's disease...
  14. pmc R loops stimulate genetic instability of CTG.CAG repeats
    Yunfu Lin
    Baylor College of Medicine, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 107:692-7. 2010
    ..DNA hybrid. These studies demonstrate that persistent hybrids between the nascent RNA transcript and the template DNA strand at CTG.CAG tracts promote instability of DNA trinucleotide repeats.
  15. ncbi Spt4 is selectively required for transcription of extended trinucleotide repeats
    Chia Rung Liu
    Institute of Biochemistry and Molecular Biology, National Yang Ming University, No 155, Section 2, Linong Street, Taipei, Taiwan, Republic of China
    Cell 148:690-701. 2012
    Lengthy trinucleotide repeats encoding polyglutamine (polyQ) stretches characterize the variant proteins of Huntington's disease and certain other inherited neurological disorders...
  16. ncbi Trinucleotide expansion in haploid germ cells by gap repair
    I V Kovtun
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, Minnesota, USA
    Nat Genet 27:407-11. 2001
    ..Expansion occurs during gap-filling synthesis when DNA loops comprising the CAG trinucleotide repeats are sealed into the DNA strand.
  17. pmc RNA structure of trinucleotide repeats associated with human neurological diseases
    Krzysztof Sobczak
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Science, Noskowskiego 12 14, 61 704 Poznan, Poland
    Nucleic Acids Res 31:5469-82. 2003
    ..We have provided experimental evidence that CCUG repeats implicated in myotonic dystrophy type 2 also form hairpin structures with properties similar to that composed of the CUG repeats...
  18. ncbi Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2
    S M Pulst
    Rose Moss Laboratory for Parkinson s and Neurodegenerative Diseases, CSMC Burns and Allen Research Institute, Los Angeles, California, USA
    Nat Genet 14:269-76. 1996
    ..In contrast to other unstable trinucleotide repeats, this CAG repeat was not highly polymorphic in normal individuals...
  19. ncbi A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length
    D R Langbehn
    Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA, USA
    Clin Genet 65:267-77. 2004
    ..This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates...
  20. ncbi Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel
    O Zhuchenko
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Genet 15:62-9. 1997
    ..We conclude that a small polyglutamine expansion in the human alpha 1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6...
  21. pmc Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats
    Kaalak Reddy
    Program of Genetics and Genome Biology, The Hospital for Sick Children, 101 College Street, East Tower, 15 312 TMDT, Toronto, Ontario M5G 1L7, Canada
    Nucleic Acids Res 39:1749-62. 2011
    ..sequences, prokaryotic and mitochondrial replication origins, and disease-associated (CAG)n and (GAA)n trinucleotide repeats. The determinants of trinucleotide R-loop formation are unclear...
  22. ncbi Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers
    C M Greco
    Department of Pathology, University of California, Davis, School of Medicine, USA
    Brain 125:1760-71. 2002
    ..The origin of the inclusions is unknown, although elevated FMR1 mRNA levels in these pre-mutation carriers may lead to the neuropathological changes...
  23. ncbi Chemotherapeutically induced deletion of expanded triplet repeats
    Vera I Hashem
    Laboratory of DNA Structure and Mutagenesis, Center for Genome Research, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, 2121 West Holcombe Blvd, Houston, TX 77030 3303, USA
    Mutat Res 508:107-19. 2002
    ..These results suggest that a chemotherapeutic approach to the reduction in triplet repeat length may provide one possible rationale to slow, stop, or reverse the progression of these diseases...
  24. ncbi Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins
    Walther J A A van den Broek
    Department of Cell Biology, UMC Nijmegen, Nijmegen Center for Molecular Life Sciences, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Hum Mol Genet 11:191-8. 2002
    ..Competition of Msh3 and Msh6 for binding to Msh2 in functional complexes with different DNA mismatch-recognition specificity may explain why the somatic (CTG)n expansion rate is differentially affected by ablation of Msh3 and Msh6...
  25. pmc Human mismatch repair protein hMutLα is required to repair short slipped-DNAs of trinucleotide repeats
    Gagan B Panigrahi
    Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada
    J Biol Chem 287:41844-50. 2012
    ..The joint involvement of hMutSβ and hMutLα suggests that repeat instability may be the result of aberrant outcomes of repair attempts...
  26. ncbi An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals
    Paula D Ladd
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Hum Mol Genet 16:3174-87. 2007
    ..Moreover, it exhibits premutation-specific alternative splicing. Taken together, these observations suggest that in addition to FMR1, ASFMR1 may contribute to the variable phenotypes associated with the CGG repeat expansion...
  27. pmc A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro
    Ed Grabczyk
    Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA 70112, USA
    Nucleic Acids Res 35:5351-9. 2007
    ..TTC tracts. RNA.DNA hybrids have a potential role in GAA.TTC tract instability and in the mechanism underlying reduced frataxin mRNA levels in Friedreich Ataxia...
  28. pmc Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis
    Yaohui Chai
    Department of Neurology, 3160 Medical Labs, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 99:9310-5. 2002
    ....
  29. pmc CAG-encoded polyglutamine length polymorphism in the human genome
    Stefanie L Butland
    UBC Bioinformatics Centre, Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    BMC Genomics 8:126. 2007
    Expansion of polyglutamine-encoding CAG trinucleotide repeats has been identified as the pathogenic mutation in nine different genes associated with neurodegenerative disorders...
  30. pmc Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy
    L T Timchenko
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Nucleic Acids Res 24:4407-14. 1996
    ..We propose that the (CUG)n repeat region in Mt-PK mRNA is a binding site for CUG-BP/hNab50 in vivo, and triplet repeat expansion leads to sequestration of this hnRNP on mutant Mt-PK transcripts...
  31. ncbi Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers
    A Kenneson
    Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hum Mol Genet 10:1449-54. 2001
    ..These biochemical deviations associated with intermediate and premutation FMR1 alleles, found in approximately 4% of the population, suggest that the phenotypic spectrum of fragile X syndrome may need to be revisited...
  32. ncbi Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice
    Alejandro Lloret
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Hum Mol Genet 15:2015-24. 2006
    ..Our findings set the stage for defining disease-related genetic pathways that will ultimately provide insight into disease mechanism...
  33. ncbi Transcription promotes contraction of CAG repeat tracts in human cells
    Yunfu Lin
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, One Baylor Plaza, Texas 77030, USA
    Nat Struct Mol Biol 13:179-80. 2006
    ..These results define a pathway for CAG.CTG repeat contraction that is initiated by transcription, depends on elements of mismatch and nucleotide-excision repair and does not require DNA replication...
  34. pmc Structural diversity of triplet repeat RNAs
    Krzysztof Sobczak
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61 704 Poznan, Poland
    J Biol Chem 285:12755-64. 2010
    ..The results of this study provide a comprehensive structural foundation for the functional analysis of triplet repeats in transcripts...
  35. ncbi CAG repeats containing CAA interruptions form branched hairpin structures in spinocerebellar ataxia type 2 transcripts
    Krzysztof Sobczak
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    J Biol Chem 280:3898-910. 2005
    ..The structural organization of the repeat interruption systems present in other human transcripts, such as SCA1, TBP, FOXP2, and MAML2, are also discussed...
  36. pmc The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at CAG/CTG repeats
    Agathi Vasiliki Goula
    Department of Neurogenetics and Translational Medicine, Institute of Genetics and Molecular and Cellular Biology IGBMC, UMR 7104 CNRS INSERM UdS, Illkirch, France
    Biochemistry 51:3919-32. 2012
    ..Our results show that the BER stoichiometry, nucleotide sequence, and DNA damage position modulate repair outcome and suggest that a suboptimal long-patch BER activity promotes CAG/CTG repeat instability...
  37. pmc Large-scale expansions of Friedreich's ataxia GAA repeats in yeast
    Alexander A Shishkin
    Department of Biology, Tufts University, Medford, MA 02155, USA
    Mol Cell 35:82-92. 2009
    ..We propose a model for large-scale repeat expansions based on template switching during replication fork progression through repetitive DNA...
  38. pmc The structural basis of myotonic dystrophy from the crystal structure of CUG repeats
    Blaine H M Mooers
    Department of Chemistry, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403 1229, USA
    Proc Natl Acad Sci U S A 102:16626-31. 2005
    ..The CUG helix is very similar in structure to A-form RNA with the exception of the unique U-U mismatches. This structure provides a high-resolution view of a toxic, trinucleotide repeat RNA...
  39. pmc Trinucleotide repeats in human genome and exome
    Piotr Kozlowski
    Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    Nucleic Acids Res 38:4027-39. 2010
    b>Trinucleotide repeats (TNRs) are of interest in genetics because they are used as markers for tracing genotype-phenotype relations and because they are directly involved in numerous human genetic diseases...
  40. pmc A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding
    Jonathan F Arambula
    Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA
    Proc Natl Acad Sci U S A 106:16068-73. 2009
    ..Ligand 1 does not destabilize the unrelated RNA-protein complexes the U1A-SL2 RNA complex and the Sex lethal-tra RNA complex. Thus, ligand 1 selectively destabilizes the MBNL1N-poly(CUG) complex...
  41. ncbi Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles
    C Dombrowski
    Unite de Recherche en Genetique Humaine et Moleculaire, Hospital St François d Assise Research Center, Department of Medical Biology, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada, G1L 3L5
    Hum Mol Genet 11:371-8. 2002
    ..The loss of AGG interruptions thus appears to be a late event that leads to greatly increased instability and may be related to the haplotype background of specific FMR1 alleles...
  42. ncbi A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease?
    R Koide
    Department of Neurology, Niigata University, Japan
    Hum Mol Genet 8:2047-53. 1999
    ..The present study provides new insights into sporadic-onset trinucleotide repeat diseases that involve de novo CAG repeat expansion...
  43. ncbi CAG repeat number is not inversely associated with androgen receptor activity in vitro
    H Nenonen
    Department of Clinical Sciences, Molecular Genetic Reproductive Medicine, Lund University, CRC, Building 91, Plan 10, SE 205 02 Malmo, Sweden
    Mol Hum Reprod 16:153-7. 2010
    ....
  44. pmc Genomic deletions and point mutations induced in Saccharomyces cerevisiae by the trinucleotide repeats (GAA·TTC) associated with Friedreich's ataxia
    Wei Tang
    Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA
    DNA Repair (Amst) 12:10-7. 2013
    Expansion of certain trinucleotide repeats causes several types of human diseases, and such tracts are associated with the formation of deletions and other types of genetic rearrangements in Escherichia coli, yeast, and mammalian cells...
  45. pmc Structural insights into CUG repeats containing the 'stretched U-U wobble': implications for myotonic dystrophy
    Agnieszka Kiliszek
    Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    Nucleic Acids Res 37:4149-56. 2009
    ..The regular hydrogen-bonding pattern of interactions with the solvent, the electrostatic charge distribution and surface features indicate the ligand binding potential of the CUG tracks...
  46. ncbi CAG repeat polymorphism in androgen receptor gene is not directly associated with polycystic ovary syndrome but influences serum testosterone levels
    L Skrgatić
    Department of Obstetrics and Gynaecology, University of Zagreb Medical School, Division of Human Reproduction, University Medical Centre Zagreb, Petrova 13, Zagreb, Croatia
    J Steroid Biochem Mol Biol 128:107-12. 2012
    ..594, P=0.095, P=0.290 and P=0.151, respectively). In conclusion, the AR CAG repeat polymorphism is not a major determinant of PCOS in the Croatian population, but it is a predictor of serum TT level variability in women with PCOS...
  47. ncbi Risk prediction for clinical phenotype in myotonic dystrophy type 1: data from 2,650 patients
    Leila Baghernajad Salehi
    Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy
    Genet Test 11:84-90. 2007
    ..This study demonstrates that measurement of triplet expansions in patients' DNA can be considered as a useful tool for DM1 phenotype assessment and presymptomatic testing...
  48. ncbi Structural and functional consequences of glutamine tract variation in the androgen receptor
    Grant Buchanan
    Dame Roma Mitchell Cancer Research Laboratories, Adelaide University Hanson Institute, SA, Australia
    Hum Mol Genet 13:1677-92. 2004
    ..That between 91 and 99% of AR alleles in different racial-ethnic groups encode a polyQ tract in the range of Q16-Q29 suggests that N/C interaction has been preserved as an essential component of androgen-induced AR signaling...
  49. ncbi Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease
    Josep M Canals
    Departament de Biologia Cel lular i Anatomia Patològica, Facultat de Medicina, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Spain
    J Neurosci 24:7727-39. 2004
    ..Hence, administration of exogenous BDNF may delay or stop illness progression...
  50. ncbi The GAA triplet-repeat is unstable in the context of the human FXN locus and displays age-dependent expansions in cerebellum and DRG in a transgenic mouse model
    Rhonda M Clark
    Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
    Hum Genet 120:633-40. 2007
    ..This mouse model will serve as a useful tool to delineate the mechanism(s) of disease-specific somatic instability in FRDA...
  51. ncbi Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon
    Melvin M Evers
    Department of Human Genetics, Leiden University Medical Center, The Netherlands
    Neurobiol Dis 58:49-56. 2013
    ..These results suggest that exon skipping may be a novel therapeutic approach to reduce polyglutamine-induced toxicity in spinocerebellar ataxia type 3. ..
  52. pmc Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes
    Vicki Whan
    CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Rd, St Lucia, Queensland 4067, Australia
    BMC Genomics 11:654. 2010
    ..A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins...
  53. ncbi Androgen receptor CAG repeats and prostate cancer
    Kevin A Nelson
    Department of Epidemiology and Biostatistics, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106 4945, USA
    Am J Epidemiol 155:883-90. 2002
    ..CAG repeat length can be determined with high sensitivity and specificity. Presently, there is no recommended population screening for AR CAG repeat length...
  54. ncbi Frequency and stability of the myotonic dystrophy type 1 premutation
    L Martorell
    Servei de Genètica, Hospital de Sant Pau, Barcelona, Spain
    Neurology 56:328-35. 2001
    ..However, the incidence of the disease appears to remain constant. It was the authors' aim to determine the frequency and germline stability of the DM1 premutation alleles that give rise to new DM1 families...
  55. pmc Correlation of inter-locus polyglutamine toxicity with CAG•CTG triplet repeat expandability and flanking genomic DNA GC content
    Colm E Nestor
    Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
    PLoS ONE 6:e28260. 2011
    ....
  56. ncbi SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene
    O Riess
    Molecular Human Genetics, Ruhr University, Bochum, Germany
    Hum Mol Genet 6:1289-93. 1997
    ..Most importantly, the trinucleotide expansion was observed in four ataxia patients without obvious family history of the disease which necessitates a search for the SCA6 (CAG)n expansion even in sporadic patients...
  57. pmc Transcription-induced DNA toxicity at trinucleotide repeats: double bubble is trouble
    Yunfu Lin
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX USA
    Cell Cycle 10:611-8. 2011
    b>Trinucleotide repeats (TNR) are a blessing and a curse...
  58. ncbi The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease
    Jiří Klempíř
    Department of Neurology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
    Mov Disord 26:125-9. 2011
    ..We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved...
  59. ncbi Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse
    J M Ordway
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 35294, USA
    Cell 91:753-63. 1997
    ..Neuronal intranuclear inclusions are present in affected mice. Our results show that CAG repeats do not need to be located within one of the classic repeat disorder genes to have a neurotoxic effect...
  60. ncbi Familial influence on age of onset among siblings with Huntington disease
    A Rosenblatt
    Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland USA
    Am J Med Genet 105:399-403. 2001
    ..A linkage study is feasible with the cooperation of a number of major centers and may be made more efficient by concentrating on sibling pairs that are highly discordant for age of onset...
  61. ncbi Standardization and statistical approaches to therapeutic trials in the R6/2 mouse
    Emma Hockly
    Department of Medical and Molecular Genetics, King s College London, Guy s Tower, Guy s Hospital, London SE1 9RT, UK
    Brain Res Bull 61:469-79. 2003
    ..Here we investigate the sources of phenotypic variability in R6/2, and make recommendations for the future use of such models in therapeutic trials...
  62. ncbi Huntington's disease: From molecular basis to therapeutic advances
    Sylvia Krobitsch
    Max Planck Institute for Molecular Genetics, Ihnestrasse 63 73, 14195 Berlin, Germany
    Int J Biochem Cell Biol 43:20-4. 2011
    ....
  63. pmc A novel approach to investigate tissue-specific trinucleotide repeat instability
    Jong Min Lee
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
    BMC Syst Biol 4:29. 2010
    ..However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors...
  64. ncbi Phenotypic heterogeneity of mutations in androgen receptor gene
    Singh Rajender
    Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India
    Asian J Androl 9:147-79. 2007
    ..Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens...
  65. ncbi An intramolecular quadruplex of (GGA)(4) triplet repeat DNA with a G:G:G:G tetrad and a G(:A):G(:A):G(:A):G heptad, and its dimeric interaction
    A Matsugami
    Department of Environment and Natural Sciences, Graduate School of Environment and Information Sciences, Yokohama National University, 79-7 Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan
    J Mol Biol 313:255-69. 2001
    ..This is in contrast to the case of d(GGAGGAN) (N=G or T), which forms a duplex under low salt concentration conditions. On the basis of these results, the structure of naturally occurring GGA triplet repeat DNA is discussed...
  66. ncbi Interactions between the Werner syndrome helicase and DNA polymerase delta specifically facilitate copying of tetraplex and hairpin structures of the d(CGG)n trinucleotide repeat sequence
    A S Kamath-Loeb
    Gottstein Memorial Cancer Research Laboratory, Departments of Pathology and Biochemistry, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 276:16439-46. 2001
    ..Our findings suggest a possible role of WRN in rescuing pol delta-mediated replication at forks stalled by unusual DNA secondary structures...
  67. ncbi Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion
    G David
    INSERM U289, Hopital de la Salpetriere, Paris, France
    Nat Genet 17:65-70. 1997
    ..SCA7 is the first such disorder in which the degenerative process also affects the retina...
  68. pmc The GAA*TTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner
    E Grabczyk
    Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 0830, USA
    Nucleic Acids Res 28:2815-22. 2000
    ..The non-template (GAA) strand folds back creating a loop in the template strand, and the polymerase is paused at the distal triplex-duplex junction...
  69. pmc CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches
    Douglas R Langbehn
    Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242 1000, USA
    Am J Med Genet B Neuropsychiatr Genet 153:397-408. 2010
    ..The Langbehn et al. model appears accurate enough to have substantial utility in various research contexts. We also emphasize remaining caveats, many of which are relevant for any direct application to genetic counseling...
  70. ncbi Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice
    K Manley
    Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, New York, USA
    Nat Genet 23:471-3. 1999
    ..16) with Msh2-/- mice. Our results show that Msh2 is required for somatic instability of the CAG repeat...
  71. ncbi Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts
    Caixia Hou
    Graduate Center for Toxicology and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, USA
    Nat Struct Mol Biol 16:869-75. 2009
    Expansion of CAG/CTG trinucleotide repeats is associated with certain familial neurological disorders, including Huntington's disease...
  72. pmc CAG expansion in the Huntington disease gene is associated with a specific and targetable predisposing haplogroup
    Simon C Warby
    Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, BC, Canada
    Am J Hum Genet 84:351-66. 2009
    ....
  73. ncbi Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo
    H Ikeda
    Department of Pharmacology, Kyoto University Faculty of Medicine, Japan
    Nat Genet 13:196-202. 1996
    ..Our results demonstrate the potential involvement of the expanded polyglutamine as the common aetiological agent for inherited neurodegenerative diseases with CAG expansions...
  74. ncbi Preparing for preventive clinical trials: the Predict-HD study
    Jane S Paulsen
    Department of Psychiatry, University of Iowa, Iowa City 52242 1000, USA
    Arch Neurol 63:883-90. 2006
    ..The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown...
  75. ncbi Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients
    K Sathasivam
    Division of Medical and Molecular Genetics, GKT School of Medicine, King's College London, UK
    Hum Mol Genet 10:2425-35. 2001
    ..An investigation of the pathological consequences of the HD mutation in these cells will provide insight into cellular basis of the disease...
  76. pmc Transcription destabilizes triplet repeats
    Yunfu Lin
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Mol Carcinog 48:350-61. 2009
    ....
  77. ncbi Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice
    C J Cummings
    Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 10:1511-8. 2001
    ..We found that high levels of HSP70 did indeed afford protection against neurodegeneration...
  78. ncbi DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing
    Alexander Saveliev
    CSC Gene Control Mechanisms and Disease Group, Experimental Genetics, Faculty of Medicine, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK
    Nature 422:909-13. 2003
    ....
  79. ncbi Imperfect CAG repeats form diverse structures in SCA1 transcripts
    Krzysztof Sobczak
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, 61 704 Poznan, Poland
    J Biol Chem 279:41563-72. 2004
    ..Thus, the interruptions destabilize the CAG repeat hairpin, which is likely to decrease its ability to participate in the putative RNA pathogenesis mechanism driven by the long CAG repeat hairpins...
  80. ncbi CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms
    S Choudhry
    Functional Genomics Unit, Centre for Biochemical Technology CSIR, Mall Road, Delhi, India
    Hum Mol Genet 10:2437-46. 2001
    ..Our study also provides new haplotypes associated with SCA2 that should prove useful in further understanding the mutational history and mechanism of repeat instability at the SCA2 locus...
  81. ncbi Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells
    John D Cleary
    Program of Genetics and Genomic Biology, The Hospital for Sick Children, 555 University Avenue, Elm Wing 11 135, Toronto, Ontario M5G 1X8, Canada
    Nat Genet 31:37-46. 2002
    ..This model system recapitulates the bias for expansions observed in many of the diseases associated with trinucleotide repeats. Our results might explain the variable amounts of CTG/CAG instability that are observed in different ..
  82. ncbi Patterns of CAG repeat interruptions in SCA1 and SCA2 genes in relation to repeat instability
    Krzysztof Sobczak
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
    Hum Mutat 24:236-47. 2004
    ..The reliable SSCP/duplex analysis presented here may be the method of choice for the systematic searching of genes for known and novel interrupted repeats...
  83. ncbi Onset and rate of striatal atrophy in preclinical Huntington disease
    E H Aylward
    Department of Radiology, University of Washington, Seattle, WA 98195, USA
    Neurology 63:66-72. 2004
    ..Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms...
  84. pmc Myotonic dystrophy: RNA pathogenesis comes into focus
    Laura P W Ranum
    Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA
    Am J Hum Genet 74:793-804. 2004
    ....
  85. pmc In vitro repair of DNA hairpins containing various numbers of CAG/CTG trinucleotide repeats
    Tianyi Zhang
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China
    DNA Repair (Amst) 11:201-9. 2012
    Expansion of CAG/CTG trinucleotide repeats (TNRs) in humans is associated with a number of neurological and neurodegenerative disorders including Huntington's disease...
  86. ncbi New anti-huntingtin monoclonal antibodies: implications for huntingtin conformation and its binding proteins
    J Ko
    Biology Division, California Institute of Technology, Pasadena, CA 91125, USA
    Brain Res Bull 56:319-29. 2001
    ..As with MW1-6, the epitopes for MW7 and 8 are differentially available in the various subcellular compartments where Htt is found...
  87. ncbi Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life
    Irene De Biase
    Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Genomics 90:1-5. 2007
    ..91; p=0.0001). Therefore, somatic instability in FRDA occurs mostly after early embryonic development and progresses throughout life, lending further support to the role of postnatal somatic instability in disease pathogenesis...
  88. pmc Trinucleotide repeat deletion via a unique hairpin bypass by DNA polymerase β and alternate flap cleavage by flap endonuclease 1
    Meng Xu
    Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA
    Nucleic Acids Res 41:1684-97. 2013
    ..Our results provide new insight into the role of BER in modulating genome stability that is associated with human diseases...
  89. ncbi Natural history of spinal-bulbar muscular atrophy
    Nizar Chahin
    Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA
    Neurology 70:1967-71. 2008
    ....
  90. ncbi Spinocerebellar ataxia type 6 in Mainland China: molecular and clinical features in four families
    Hong Jiang
    Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
    J Neurol Sci 236:25-9. 2005
    ..In the 4 families with SCA6, we found significant anticipation in the absence of genetic instability on transmission. This is the first report of geographic cluster of families with SCA6 subtype in Mainland China...
  91. ncbi Context dependence of trinucleotide repeat structures
    Natalya N Degtyareva
    Department of Chemistry, Furman University, Greenville, South Carolina 29613, USA
    Biochemistry 49:3024-30. 2010
    ..Thus, an open (CAG)(8) loop and exposed bases in the arms indicate that the strand junction profoundly influences repeated sequences within three-way junctions...
  92. pmc Sequence length dictates repeated CAG folding in three-way junctions
    Natalya N Degtyareva
    Department of Chemistry, Furman University, Greenville, SC 29613, USA
    Biochemistry 50:458-65. 2011
    ....
  93. ncbi Clinical and neuroradiological features of patients with spinocerebellar ataxias from Korean kindreds
    Oh Young Bang
    Departments of Neurology and Medical Genetics, School of Medicine, Ajou University, Suwon, South Korea
    Arch Neurol 60:1566-74. 2003
    ..Comparative studies of clinical and magnetic resonance imaging findings in patients with spinocerebellar ataxias (SCAs) have been seldom reported...
  94. ncbi The nonrandom distribution of long clusters of all possible classes of trinucleotide repeats in barley chromosomes
    Angeles Cuadrado
    Department of Cell Biology and Genetics, University of Alcala, 28871 Alcala de Henares, Madrid, Spain
    Chromosome Res 15:711-20. 2007
    ..and (GCC)5, was used to characterize the nonrandom and motif-dependent distribution of tandem arrays of trinucleotide repeats in the metaphase chromosomes and interphase nuclei of barley (Hordeum vulgare L.)...
  95. ncbi Molecular architecture of CAG repeats in human disease related transcripts
    Gracjan Michlewski
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14 St, 61 704 Poznan, Poland
    J Mol Biol 340:665-79. 2004
    ....
  96. pmc Genetic analysis of the GRIK2 modifier effect in Huntington's disease
    Wenqi Zeng
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
    BMC Neurosci 7:62. 2006
    ....
  97. ncbi Hypospadias and the androgen receptor gene: mutation screening and CAG repeat length analysis
    K Muroya
    Department of Paediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan
    Mol Hum Reprod 7:409-13. 2001
    ..The results suggest that AR gene abnormalities do not constitute a major factor in the development of hypospadias...
  98. ncbi Large normal and reduced penetrance alleles in Huntington disease: instability in families and frequency at the laboratory, at the clinic and in the population
    J Sequeiros
    UnIGENe, IBMC Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal
    Clin Genet 78:381-7. 2010
    ..This reinforces the need to understand the genomic context of repeat instability in each family and population...
  99. ncbi Structural studies of a trinucleotide repeat sequence using 2-aminopurine
    Natalya N Degtyareva
    Department of Chemistry, Furman University, Greenville, South Carolina 29613, USA
    Biochemistry 48:2340-6. 2009
    ..These results provide the basis to interpret the structures adopted by other repeated (CAG) structures...
  100. ncbi Simple sequence repeats in proteins and their significance for network evolution
    John M Hancock
    Bioinformatics Group, MRC Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK
    Gene 345:113-8. 2005
    ..We outline a conceptualization of how protein SSRs may arise and become fixed in proteins during evolution, and suggest that emergence and change in length of protein SSRs may affect the topology of protein interaction networks...
  101. pmc POLG1 polyglutamine tract variants associated with Parkinson's disease
    Johanna Eerola
    Department of Neurology, Helsinki University Central Hospital, FIN 00290 Helsinki, Finland
    Neurosci Lett 477:1-5. 2010
    ..Other large case-control studies and analyses on functional differences of POLG1 poly-Q variants are warranted...

Research Grants63

  1. TRINUCLEOTIDE REPEATS AND NEUROLOGIC DISEASE
    Russell Margolis; Fiscal Year: 2004
    ..atrophy; and spinal and bulbar muscular atrophy) are now known to be caused by expansions of CAG/CTG trinucleotide repeats. The P.I...
  2. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..genome that stall replication include difficult-to-replicate DNA regions such as telomeres, fragile sites, trinucleotide repeats and centromeric DNA. At these regions, the replisome must be restarted after stalling...
  3. Second-site genetic modifiers of CTG/CAG microsatellite stability
    Michael Leffak; Fiscal Year: 2013
    ..phenotypes in other organs, the molecular trigger of disease is an increase in the number of CTG/CAG trinucleotide repeats in the 3'UTR of the DMPK gene...
  4. Exosome based therapeutics in Huntington's disease
    Neil Aronin; Fiscal Year: 2013
    ..Huntington's disease (HD) is caused by an increase in the CAG trinucleotide repeats to [unreadable] 36 in series;it necessitates years in a high level nursing facility because of ..
  5. Amplification Strategies for Detection of Fragile X Gene Trinucleotide Repeats
    Andrew G Hadd; Fiscal Year: 2011
    ..This will enable widespread screening to identify carriers and permit earlier diagnosis and intervention for Fragile X Syndrome patients. ..
  6. CCCTC-binding factor (CTCF) in trinucleotide repeat instability and disease
    Albert R La Spada; Fiscal Year: 2010
    Despite significant advances in our understanding of how trinucleotide repeats cause disease, mechanisms underlying their unique property of genetic instability remain ill-defined...
  7. Mouse Models to Define Critical Periods and Molecular Targets in FXTAS
    Robert F Berman; Fiscal Year: 2013
    ..The Fragile X gene (FMR1) is polymorphic for the number of CGG trinucleotide repeats in the 5'-untranslated region. Repeat sizes in the general population range between 5-55 CGG repeats...
  8. FMR 1-SLS: Improving Fragile X diagnosis using amplification-free single locus ta
    STEPHEN WHITFIELD TURNER; Fiscal Year: 2013
    ..SMRT(R)) Sequencing has the ability to read through virtually any DNA sequence context (including trinucleotide repeats of CGG), produces reads averaging almost 5000 bases in length, and intrinsically produces information ..
  9. Allele-Selective Inhibitors for Expanded Trinucleotide Repeat Genes
    David R Corey; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Background. Expanded trinucleotide repeats cause Huntington's Disease (HD) and other degenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed...
  10. Targeting trinucleotide repeats-induced transcriptional silencing in Friedreich's
    Marek Napierala; Fiscal Year: 2011
    ..Results of this study may also be applicable in the development of innovative therapeutic approaches for Fragile X syndrome and other neurological diseases as well as cancer. ..
  11. Amplification Strategies for Detection of Fragile X Trinucleotide Repeats
    ANDREW HADD; Fiscal Year: 2009
    ..This will enable widespread screening to identify carriers and permit earlier diagnosis and intervention for Fragile X Syndrome patients. ..
  12. DNA CONFORMATION, TRIPLET EXPANSION, AND HUMAN DISEASE
    Robert Wells; Fiscal Year: 1999
    ..The mutations found in each of these disorders involve increased lengths of trinucleotide repeats (CGG and CTG) which are genetically unstable...
  13. Fragility and Instability at Hairpin-Forming Trinucleotide Repeats in Yeast
    Catherine H Freudenreich; Fiscal Year: 2010
    ....
  14. DNA EXPANSION IN SCHIZOPHRENIA
    Cynthia McMurray; Fiscal Year: 2000
    ..severity and earlier onset of disease in successive generations and is caused by expansion of simple trinucleotide repeats. It is our hypothesis that if anticipation occurs in a subset of schizophrenics, then the disrupted gene ..
  15. NMR OF TRINUCLEOTIDE REPEATS--NEURODEGENERATIVE DISEASE
    Xiaolian Gao; Fiscal Year: 1999
    ..Studies of structural transitions as a function of chain length. ..
  16. SOLUTION STRUCTURE AND DYNAMICS OF NUCLEIC ACIDS
    Thomas James; Fiscal Year: 2001
    ..the related pseudosquare knot DNA structures are potentially formed with short direct repeats; while some trinucleotide repeats have been associated with genomic instability leading to diseases such as myotonic dystrophy, somewhat ..
  17. MUTATIONS INDUCED IN HUMAN SPERM BY CANCER THERAPY
    Marvin Meistrich; Fiscal Year: 1999
    ..analysis will be performed at the mini-satellite M5205, M532, and CEB1 loci and at the microsatellite trinucleotide repeats associated with the myotonic dystrophy and Huntington disease loci and the androgen receptor gene...
  18. TRINUCLEOTIDE REPEATS, NEURODEVELOPMENT, AND DISEASE
    Russell Margolis; Fiscal Year: 1999
    b>Trinucleotide repeats consist of three bases consecutively repeated (e.g., CAG CAG CAG CAG CAG CAG CAG) within a region of genomic DNA...
  19. Polymorphisms of Neural NOS and the Asthma Phenotype
    Michael Wechsler; Fiscal Year: 2005
    ..reviewed herein suggest that mild asthmatics who harbor NOS1 alleles with a greater number of intronic trinucleotide repeats have lower and less variable levels of expired NO...
  20. TRI-NUCLEOTIDE REPEAT AND FRAGILE SITES IN YEAST
    Virginia Zakian; Fiscal Year: 2002
    ..abstract): An ever-increasing number of human genetic diseases are attributed to expansion of trinucleotide repeats (TNRs)...
  21. STRUCTURE SPECIFIC NUCLEASES IN GENOMIC INSTABILITY
    Min Park; Fiscal Year: 2001
    ..The specific aims of this study are: 1) to evaluate the FEN-1's ability to process trinucleotide repeats in vitro...
  22. TRIPLET REPEAT INSTABILITY IN YEAST AND HUMAN CELLS
    Tadayoshi Bessho; Fiscal Year: 2007
    ..In addition to their medical relevance, the genetics of trinucleotide repeats (TNRs) are unique and complex...
  23. GENETIC INSTABILITY AND TRIPLET REPEAT DISEASES IN AGING
    MYRON GOODMAN; Fiscal Year: 2002
    ..on exploring an important human genomic problem, the biochemical and genetic basis for expansions of trinucleotide repeats associated with neurological diseases...
  24. Fragile X Syndrome: Banbury Conferences
    William T Greenough; Fiscal Year: 2010
    ..It arises due to expansion of an unstable region of trinucleotide repeats in the 5'untranslated promoter region of the FMR-1 gene, causing hypermethylation of cytosine ..
  25. Instability of Triplet Repeats in Mammalian Cells
    Leroy Hubert; Fiscal Year: 2009
    Repetitive sequences exist through out the human genome. Trinucleotide repeats represent an important subset of these genomic elements...
  26. Replication Through CAG Trinucleotide Repeat Tracts
    DENNIS LIVINGSTON; Fiscal Year: 2004
    ..on the steps of DNA replication that are important in maintaining the stability of long tracts of CAG trinucleotide repeats. Long CAG repeat tracts are found in some human genes and are the mutational cause of over a dozen ..
  27. Small Molecules as Modulators of Polyglutamine Aggregation
    Valerie Berthelier; Fiscal Year: 2009
    ..inherited neurological disorders that are caused by a DNA abnormality: the presence of additional CAG trinucleotide repeats in the disease gene...
  28. REACTION OF CARCINOGENS WITH DNA AND BIOLOGICAL EFFECTS
    YOSHINORI KOHWI; Fiscal Year: 1999
    ..A genetic instability that produces an expansion of trinucleotide repeats has been observed in several hereditary diseases...
  29. NEURODEGENERATIVE DISORDER ANALYSIS USING IR-MALDI-MS
    NELLI TARANENKO; Fiscal Year: 2000
    ..PROPOSED COMMERCIAL APPLICATIONS: The analysis of genes containing CAG trinucleotide repeats & microsatellite markers...
  30. EFFECTS OF HUNTINGTON ON GENE TRANSCRIPTION
    Dimitri Krainc; Fiscal Year: 2004
    ..These mutations are expansions of a polyglutamine repeat motif (coded by CAG trinucleotide repeats in the mRNA) within the protein, making HD one of several known "glutamine repeat disorders"...
  31. FUNCTION OF THE DRPLA GENE PRODUCT ATROPHIN
    Craig Blackstone; Fiscal Year: 2001
    ..These mutations are expansions of a polyglutamine repeat motif (coded by CAG trinucleotide repeats in the mRNA) within the protein, making DRPLA one of several known "glutamine repeat disorders...
  32. Response of a Sample Population with the Deleterious HD allele RESPOND-HD
    Jane Paulsen; Fiscal Year: 2007
    ..This study will be among the first to compare ethical, legal and social experiences of having known genetic risk. ..
  33. Fragile X-associated Tremor/Ataxia Syndrome
    Paul Hagerman; Fiscal Year: 2009
    ..Thus, knowledge of the mechanisms leading to the inclusions in FXTAS, as a single-gene disorder, should lead to a broader understanding of the events leading to inclusion formation in other neurodegenerative disorders. ..
  34. PROTEIN NUCLEIC ACID INTERACTIONS
    Paul Hagerman; Fiscal Year: 2002
    ..The RNA target is likely to possess a significant degree of flexibility prior to protein binding, thus providing a test of the TEB/LRET approach to assess flexibility. ..
  35. Huntington's Disease:Morphometry, Chemistry & Cognition
    HERMINIA ROSAS; Fiscal Year: 2002
    ..This work will advance our understanding of the functional consequences of the genetic mutation in HD and may lead to improvements in monitoring and treating the disease. ..
  36. NEUROPSYCHOLOGY AND DEMENTIA
    Jane Paulsen; Fiscal Year: 2002
    ..This award will facilitate the candidate's research efforts towards understanding brain-behavior relations in dementia and using this knowledge to assist families and individuals in treatment planning for the future. ..
  37. Neurological Phenotype in FMR1 Premutation Carriers
    Paul Hagerman; Fiscal Year: 2005
    ..The project will also include an analysis of association of the phenotype with a newly described molecular abnormality of the premutation range (elevated FMR1 mRNA). ..
  38. Chemotherapy & Cognition in Older breast Cancer Patients
    James Grigsby; Fiscal Year: 2008
    ..The results could have important implications for decision-making about adjuvant chemotherapy, will further delineate the scope and nature of this problem, and could provide data useful in neuroprotective interventions. ..
  39. Mechanisms of Genetic Instabilites of Triplet Repeats
    Robert Wells; Fiscal Year: 2005
    ..In summary, the principal investigator will investigate the molecular mechanisms (replication, recombination, repair) that cause genetic instabilities in simple repeat sequences. ..
  40. Action tremor & dementia in male carriers of fragile X
    James Grigsby; Fiscal Year: 2007
    ..abstract_text> ..
  41. CARDIOVASCULAR RESEARCH TRAINING
    Douglas Zipes; Fiscal Year: 2003
    ..In addition, the program is ideally suited to effectively recruit under-represented minorities. We proposed to train 3 postdoctoral Fellows each year for 2 years as part of this grant. ..
  42. GAA TTC STRUCTURES--FUNCTIONS AND FRIEDREICHS ATAXIA
    Robert Wells; Fiscal Year: 2002
    ..TTC and their effect on transcription and on genetic instabilities (replication and recombination). ..
  43. Mistargeting of Elastase in Bone Marrow Failure
    Marshall Horwitz; Fiscal Year: 2008
    ..1 Determine if ELA2 promoter variation contributes to neutropenia; 3.2 Measure the frequency of the ELA2 C-199A allele in individuals of African descent with benign ethnic neutropenia; 3.3 Identify new neutropenia genes. ..
  44. The Role of Fragile Sites in RET/PTC Rearrangement
    Yuh Hwa Wang; Fiscal Year: 2010
    ..ugh the mechanism of chromosomal rearrangements. ..
  45. Cannabinoid Mechanisms in Human Gastrointestinal Motor and Sensory Functions
    MICHAEL L CAMILLERI; Fiscal Year: 2010
    ..These actions may be relevant to develop new treatments for IBS. The studies will also provide further understanding of the potential of medications like medical marijuana on stomach function that may be relevant to appetite control. ..
  46. INCLUSION BODY MYOSITIS: PILOT STUDY OF B-INTERFERON 1A
    Rabi Tawil; Fiscal Year: 2002
    ..The testing methods have been validated by the investigators in other studies of muscle disease. The information obtained in this study will be essential for the effective design and conduct of pivotal trials in IBM. ..
  47. PREQUEL Study In PRE-manifest HD of CoQ10/UbiquinonE Leading to Preventive Trials
    Christopher A Ross; Fiscal Year: 2010
    ....
  48. Purchase of Technai 12 TEM/STEM Electron Microscope
    Jack Griffith; Fiscal Year: 2002
    ..abstract_text> ..
  49. A COLLABORATIVE GENOMIC STUDY OF BIPOLAR DISORDER
    Wade Berrettini; Fiscal Year: 2007
    ..Analysis of the existing sib pair families plus this large set of cases and controls should permit the confirmation of several vulnerability genes during this grant period. ..
  50. MOLECULAR ANALYSIS OF HOTSPOTS OF GENETIC RECOMBINATION
    Gerald Smith; Fiscal Year: 2007
    ..Thus, the basic research proposed here will add to the foundations for understanding, diagnosing, preventing, and curing human disease. ..
  51. Large Loop DNA Repair in Yeast
    Robert Lahue; Fiscal Year: 2005
    ..abstract_text> ..
  52. Neurobehavioral correlates of bipolar disorder
    BRIAN O DONNELL; Fiscal Year: 2006
    ..abstract_text> ..
  53. Alcoholism risk and protective factors in Trinidad
    Cindy Ehlers; Fiscal Year: 2006
    ..Study findings can be compared to similar studies being conducted in the US. We believe these studies will allow for the identification of risk and protective factors for alcoholism in these islands. [unreadable] [unreadable]..
  54. MOLECULAR GENETIC CHARACTERIZATION OF SCA7
    Harry Orr; Fiscal Year: 2002
    ..To gain insight into ataxin-7 function a series of experiments are proposed to characterize the cellular and subcellular expression of ataxin-7 and to identify proteins that interact with ataxin-7 using the yeast two-hybrid system. ..
  55. Transcriptional Integration of Metabolism
    ELTON YOUNG; Fiscal Year: 2007
    ..abstract_text> ..
  56. Neurodegeneration and Polyglutamine Toxicity DRPLA
    Christopher Ross; Fiscal Year: 2007
    ..Proteolytic cleavage would be an especially good target for therapeutic interventions. [unreadable] [unreadable]..
  57. STRUCTURAL AND FUNCTIONAL ANALYSES OF NEURONAL PTPS
    Paul Lombroso; Fiscal Year: 2008
    ..STEP knock-out mice will also be characterized. The proposed investigations will be done in the supportive environment of the Child Study Center with its commitment to cliniclaly informed basic science research. ..
  58. Fragile X Premutations Among Women Diagnosed with Diminished Ovarian Reserve
    Lisa Pastore; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  59. MOLECULAR STUDIES OF CANCER SPECIFIC FRAGILE SITES
    Yuh Hwa Wang; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  60. The PTP, STEP, Regulates Amphetamine Actions
    Paul Lombroso; Fiscal Year: 2008
    ..We show preliminary feasibility data on this approach. A complementary set of experiments will study the STEP knock-out mouse that we predict is hypersensitive to stimulant treatment. ..
  61. Phenotypic Markers in Females with Fragile X Premutation
    Ave Lachiewicz; Fiscal Year: 2002
    ..In the future, larger studies will be planned to correlate these findings with other markers such as FMR1 protein and messenger RNA. ..
  62. MOLECULAR GENETICS OF THE SCA1 LOCUS
    Harry Orr; Fiscal Year: 2003
    ..Understanding the importance of these factors for SCA1 pathogenesis should provide insights for polyglutamine diseases in general. ..