AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesInformation ScienceHealth Care
Trinucleotide Repeat ExpansionTrinucleotide RepeatsFriedreich AtaxiaDNA Repeat ExpansionSpinocerebellar DegenerationsMyotonic DystrophyFragile X SyndromeHuntington DiseaseFragile X Mental Retardation ProteinIron-Binding ProteinsNeurodegenerative DiseasesAllelesMutationRepetitive Sequences, Nucleic AcidSpinocerebellar AtaxiasMachado-Joseph DiseaseHeredodegenerative Disorders, Nervous SystemNerve Tissue ProteinsBase SequenceFrontotemporal DementiaMolecular Sequence DataGenomic InstabilityAnticipation, GeneticFlap EndonucleasesMicrosatellite RepeatsDNANucleic Acid ConformationPedigreeInverted Repeat SequencesIntranuclear Inclusion BodiesAmyotrophic Lateral SclerosisMinisatellite RepeatsCerebellar AtaxiaAge of OnsetTandem Repeat SequencesChromosome FragilityMuscular Dystrophy, OculopharyngealRNA-Binding ProteinsGenetic Diseases, InbornPolymerase Chain ReactionNuclear ProteinsPolymorphism, GeneticMice, TransgenicPeptidesPhenotypeDisease Models, AnimalBrainProteinsDNA RepairSequence Analysis, DNAModels, GeneticReceptors, AndrogenGenotypeMyoclonic Epilepsies, ProgressiveDNA PrimersNerve DegenerationGenes, DominantAmino Acid SequenceNeuronsTranscription, GeneticGenome, HumanRNA, MessengerExonsDNA-Binding ProteinsHeterozygoteAtaxiaDNA ReplicationRepetitive Sequences, Amino AcidSaccharomyces cerevisiaeGenetic MarkersMutS Homolog 2 ProteinCell LineNucleic Acid HeteroduplexesFrontotemporal Lobar DegenerationGenetic VariationGene Frequency
DiseasesAutosomalMutationDisordersProteinsPhenotypeExonCaused by an expanded CAG repeatCytosine-adenine-guanineDiseaseIT15GeneticOnsetAbnormalMutationsSpinocerebellarBrainMutantAllelesProtein huntingtinChromosomeInstabilityWild-type huntingtinSpecific genesPathologyPolyglutamine expansionTripletGlutamineNeurotoxicPhenotypicSpermIndividualsTissueAtaxiaOccurAmyotrophic Lateral SSequenceSpecificityGenomeAminoMiceMethylationMolecular Genetics
Diseases22
  • The large number of genes and the diversity of processes involved in the progression of neurological diseases in general, and HD in specific, emphasizes the need for comprehensive approaches in additional to studies of individual genes 14 . (nature.com)
  • Neurodegenerative diseases are characterized by the progressive loss of cells in the central nervous system. (biologie-uni-siegen.de)
  • While some neurodegenerative diseases occur sporadically, others are caused by genetic mutations. (biologie-uni-siegen.de)
  • The so-called CAG repeat diseases are characterized by symptoms such as the progressive loss of cognitive abilities and progressive movement disorders. (biologie-uni-siegen.de)
  • Interestingly, the same protein complex promotes pathology in other diseases including sporadic neurodegenerative diseases, suggesting that deregulation of common cellular pathways may contribute to development of otherwise unrelated diseases. (biologie-uni-siegen.de)
  • Knowledge on these demethylases has led to a tremendous progress in the understanding of methyl marks in gene regulation and role in numerous diseases. (cmbn.no)
  • Analysis of polyglutamine-coding repeats in the TATA-binding protein in different neurodegenerative diseases. (cdc.gov)
  • We provide a new candidate mechanism for modulating the pathogenesis of neurodegenerative diseases sensitive to protein dosage. (nih.gov)
  • Coenzyme Q10 (CoQ10), a well-known antioxidant, has been explored as a treatment in several neurodegenerative diseases, but its utility in spinocerebellar ataxia type 3 (SCA3) has not been explored. (bvsalud.org)
  • Neurodegenerative disorders such as for example spinocerebellar ataxias (SCAs) and Alzheimer's disease (AD) represent an enormous medical and medical question however the molecular mechanisms of the diseases remain not yet determined. (ampkpathway.com)
  • HD is a member of a family of neurodegenerative diseases caused by CAG/polyglutamine expansions, which include spinobulbar muscular atrophy (SBMA), spinocerebellar ataxias (SCA) types 1, 2, 3, 6, and 7, and dentatorubral-pallidoluysian atrophy. (bmj.com)
  • Our laboratory uses genetic, cell biological, and biochemical approaches to explore the pathogenesis of polyglutamine neurodegenerative diseases, the function of Math1 in neurodevelopment, and how MECP2 mutations cause postnatal neurodevelopmental disorders. (bcm.edu)
  • Kao, C.L. Ageing and neurodegenerative diseases. (benthamscience.com)
  • Filip, M. Oxidative stress in neurodegenerative diseases. (benthamscience.com)
  • Zuo, L. Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications. (benthamscience.com)
  • We now know those structures are very relevant to many critical biological processes like gene regulation, expression of telomerase and telomere maintenance, understanding of growth/oncogenes like C-myc, understanding of organismic development, comprehension of certain enigmatic diseases like ALS and possible new cancer treatments. (anti-agingfirewalls.com)
  • Today I'm going to tell you about microsatellites, and trinucleotide repeat expansions diseases. (hstalks.com)
  • The other key point of the slide is to show that these diseases are typically either neurological, neurodegenerative, or neuromuscular. (hstalks.com)
  • Medical professionals classify both conditions as neurodegenerative diseases - conditions in which a person's brain or nerve cells gradually degrade. (medicalnewstoday.com)
  • Microsatellite and trinucleotide repeat expansion diseases [electronic resource] / David C. Rubinsztein. (ac.ke)
  • AFFiRiS is a clinical-stage biotechnology company located in Vienna, Austria, with a vision of using the immune system to identify and target human proteins central to the development and progression of chronic diseases, based on its proprietary patented AFFITOME® technology. (affiris.com)
  • The MSH3 gene encodes a DNA mismatch repair protein important in certain cancer types and in certain neurodegenerative diseases. (cancertools.org)
Autosomal7
  • Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). (geneticsmr.com)
  • HD is an autosomal dominant inherited neurodegenerative disease that becomes manifest in midlife and causes progressive motor, psychiatric, and cognitive dysfunction. (jci.org)
  • Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein 1 . (nature.com)
  • Huntington's disease (HD) is an autosomal dominant neurodegenerative condition associated with abnormal movements, cognitive deterioration, and psychiatric symptoms. (bmj.com)
  • Huntington's disease (HD) is the most prevalent autosomal dominant, trinucleotide repeat neurodegenerative disease. (grantome.com)
  • Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations, which usually manifests at around 40 to 50 years of age. (upmc.com)
  • Huntington disease (HD) is a genetic, autosomal dominant, neurodegenerative disorder characterized clinically by disorders of movement, progressive dementia, and psychiatric and/or behavioral disturbance. (medscape.com)
Mutation14
  • CAG repeats that exceed thirty-five can cause a gain-of-function mutation in ATN1. (wikipedia.org)
  • YBM12-A and YBM12-B). This mutation in leaf color is controlled by a single dominant nuclear gene. (geneticsmr.com)
  • Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. (nature.com)
  • The causative mutation is a (CAG) n trinucleotide repeat expansion of more than 35 repeats, which is translated into an abnormally long polyglutamine tract in the huntingtin protein. (bmj.com)
  • 2 The polyglutamine expansion mutation causes disease by conferring a novel deleterious function on the mutant protein and the severity correlates with increasing CAG repeat number and expression levels in transgenic mice and in cell culture models. (bmj.com)
  • The huntingtin gene encodes a protein of 350 kD;the disease causing mutation is an expansion of an amino-terminal polyglutamine repeat of more than 36 successive glutamines. (grantome.com)
  • In collaboration with Harry Orr's group (University of Minnesota), we determined that the mutation responsible for SCA1 is an expansion of a CAG trinucleotide repeat encoding glutamine in the protein Ataxin-1. (bcm.edu)
  • The mutation leads to the abnormal expansion of the production of the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly referred to as mutant Huntingtin. (benthamscience.com)
  • TTC expansion mutation is to reduce expression of frataxin at the level of transcription ( 3 ), through the formation of heterochromatin and subsequent gene silencing ( 4 - 8 ). (frontiersin.org)
  • Huntington's disease is a neurodegenerative disorder caused by a mutation on the HD gene, producing a polyglutamin (polyQ) expansion on the N-terminus of Htt. (novusbio.com)
  • For instance, if you've got a mutation caused by triplet repeat expansion, for instance in the Huntington's gene, where the trinucleotide repeats a CAG, you might have 17 CAGs in a normal chromosome. (hstalks.com)
  • Some occur in the coding region of the gene, others occur in the five prime region and others occur in the three prime region, and these have different consequences on the function of the gene and the results of the mutation. (hstalks.com)
  • Single-nucleotide polymorphism rs3849942 is associated with ALS, tagging a hexanucleotide repeat mutation in the C9orf72 gene. (ox.ac.uk)
  • These results indicate residual association at the C9orf72 locus suggesting a second disease-causing repeat mutation. (ox.ac.uk)
Disorders11
  • Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. (uni-muenchen.de)
  • Although each of the CAG repeat expansion disorders is rare, together they represent one of the most common forms of inherited neurodegeneration. (biologie-uni-siegen.de)
  • Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. (shengsci.com)
  • Andrew, S.E., Goldberg, Y.P. & Hayden, M.R. Rethinking genotype and phenotype correlations in polyglutamine expansion disorders. (nature.com)
  • The spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by a progressive loss of balance and coordination, and eventually the inability to coordinate swallowing and breathing. (bcm.edu)
  • Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer's dementia and Parkinson's disease. (preprints.org)
  • Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. (preprints.org)
  • Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. (ucl.ac.uk)
  • Next-generation sequencing of the whole exome is useful for testing for multiple candidate genes simultaneously or for discovering new, rare disorders. (medlink.com)
  • Whole exome sequencing is not suitable for detecting polynucleotide repeat disorders or large insertion/deletions. (medlink.com)
  • HD supposedly can cause psychiatric disorders in 2 ways: (1) by the direct action of the gene on striatal neurons, and (2) by the indirect effect of the disordered family environment on the children, regardless of whether they inherited the HD gene. (medscape.com)
Proteins6
  • A transcriptional co-repressor is a protein that indirectly suppresses the activity of specific genes by interacting with DNA-binding proteins. (wikipedia.org)
  • When translated into protein the CAG repeat encodes for a polyglutamine stretch in the disease-causing proteins. (biologie-uni-siegen.de)
  • In our studies we have identified a set of proteins that aberrantly bind to mutant CAG repeats. (biologie-uni-siegen.de)
  • This abnormal binding can lead to both: a loss of physiological function of the RNA-binding proteins and a gain of function of these proteins at the mutant CAG repeat RNA. (biologie-uni-siegen.de)
  • For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (wikipedia.org)
  • In collaboration with Stanley Qi and the laboratories of Wendell Lim , Jonathan Weissman , and Adam Arkin , we pioneered the engineering of CRISPR-Cas proteins for new purposes by converting Cas9 into a tool for targeted control of gene expression, referred to as CRISPR interference (CRISPRi). (berkeley.edu)
Phenotype2
  • Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. (cdc.gov)
  • Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. (acog.org)
Exon7
  • 35) in the first exon of the huntingtin ( HTT , IT15 ) gene 1 . (nature.com)
  • Exon 1 contains a CAG trinucleotide repeat that encodes the amino acid glutamine, followed by another repeat that encodes proline. (jci.org)
  • METHODS We cotransfected neuronal (SK-N-SH, human neuroblastoma) and non-neuronal (COS-7, monkey kidney) cell lines with HD exon 1 (containing either 21 or 72 CAG repeats) construct DNA and either full length wild type huntingtin or pFLAG (control vector). (bmj.com)
  • RESULTS Full length wild type huntingtin significantly reduced cell death resulting from the mutant HD exon 1 fragments containing 72 CAG repeats in both cell lines. (bmj.com)
  • Wild type huntingtin did not significantly modulate cell death caused by transfection of HD exon 1 fragments containing 21 CAG repeats in either cell line. (bmj.com)
  • HTT is the gene implicated in HD and contains a normally polymorphic trinucleotide CAG repeat region in the first exon. (upmc.com)
  • Exon 2 of the MSH3 gene was targeted by CRISPR/Cas9. (cancertools.org)
Caused by an expanded CAG repeat1
  • Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. (nature.com)
Cytosine-adenine-guanine4
  • Huntington disease (HD) is caused by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats within the HTT gene. (arupconsult.com)
  • Individuals with intermediate alleles (27-35 cytosine-adenine-guanine [CAG] repeats) typically do not have symptoms of Huntington disease (HD). (arupconsult.com)
  • Polymerase chain reaction (PCR) testing and size analysis for an expanded number of cytosine-adenine-guanine (CAG) trinucleotide repeats in the HTT gene may be performed for both symptomatic individuals and asymptomatic individuals with a family history of HD. (arupconsult.com)
  • The expansion of the cytosine-adenine-guanine (CAG) trinucleotide in the HTT gene leads to the production of atypical protein. (medicalnewstoday.com)
Disease34
  • In order to identify genes that may modify disease onset and progression, genome-wide association and gene expression studies have been performed 12 , 13 . (nature.com)
  • Variation within the Huntington's disease gene influences normal brain structure. (uni-muenchen.de)
  • Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. (uni-muenchen.de)
  • We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. (uni-muenchen.de)
  • REVIEW-ARTICLE Intermediate alleles of Huntington's disease HTT gene in different populations worldwide: a systematic review. (geneticsmr.com)
  • BACKGROUND: Spinocerebellar ataxia 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by the expansion of the trinucleotide repeat region within the ATXN3/MJD gene. (bvsalud.org)
  • Huntington disease (HD) is a progressive, hereditary, neurodegenerative disorder that is characterized by abnormalities in motor skills, cognitive skills, and psychiatric changes. (arupconsult.com)
  • Rats transgenic for Huntington's disease (tgHD51 CAG rats), surviving up to two years, represent an animal model of HD similar to the late-onset form of human disease. (hindawi.com)
  • The age of onset of the disease varies inversely with the number of CAG repeats. (jci.org)
  • A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. (nature.com)
  • Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. (nature.com)
  • Inactivation of the mouse Huntington's disease gene homolog hdh . (nature.com)
  • Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. (nature.com)
  • Trottier, Y., Biancalana, V. & Mandel, J.L. Instability of CAG repeats in Huntington's disease: relation to parental transmission and age of onset. (nature.com)
  • Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. (nature.com)
  • Because HD is an inherited disease, we expected that the mutant allele will differ from wild-type by at least a single nucleotide polymorphism, thereby offering a target for gene silencing by RNAi. (grantome.com)
  • This proposal addresses treatment of HD through study of basic mechanisms of silencing the gene that causes the disease. (grantome.com)
  • Huntington's disease is a genetic neurological disorder caused by a repeated expansion of the CAG trinucleotide, causing instability in the N-terminal of the gene coding for the Huntingtin protein. (benthamscience.com)
  • The penetrance of the CAG expansion is not complete, therefore showing variability in the severity of disease symptoms. (upmc.com)
  • Individuals with a CAG repeat size of 30 to 35 do not manifest Huntington's Disease themselves, however, the risk that their offspring will develop HD may be increased, particularly from paternal transmission of the gene. (upmc.com)
  • Detection of CAG expansions in the HTT gene that lead to Huntington's Disease. (upmc.com)
  • Huntingtin Antibody was prepared from whole rabbit serum produced by repeated immunizations with a synthetic peptide corresponding to the C-terminus of human Huntingtin disease protein. (novusbio.com)
  • Huntingtin protein (Htt) is a 348 kDa protein product of Huntington's disease (HD, IT15) gene. (novusbio.com)
  • Parkinson's disease and Huntington's disease both involve the central nervous system and are neurodegenerative, which means they cause the gradual death of nerve cells. (medicalnewstoday.com)
  • Huntington's disease is genetic , involving the Huntingtin (HTT) gene. (medicalnewstoday.com)
  • The higher the number of CAG repeats, the earlier the age of onset and the greater the severity of the disease. (medicalnewstoday.com)
  • This means that a change in only one of a person's two copies of the HTT gene can cause the disease. (medicalnewstoday.com)
  • When someone with Huntington's disease has children, each child has a 1 in 2 chance of inheriting the mutated gene and developing the disease. (medicalnewstoday.com)
  • Huntington's Disease (HD) is a neurodegenerative disease, caused by the expansion of an unstable (CAG) n in the HTT gene. (siu.edu.ar)
  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons. (ox.ac.uk)
  • Huntington disease (HD) is associated with an excessive sequence of CAG repeats in the 5' end of HTT (alias IT15- interesting transcript number 15), a 350-kD gene located on the short arm of chromosome 4. (medscape.com)
  • Approximately 55 percent were felt to have a single progressive neurodegenerative etiology, predominantly Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), dementia related to Parkinson disease (PD), and corticobasal degeneration (including corticobasal syndrome and many other phenotypes) [ 2 ]. (medilib.ir)
  • Mechanisms of human genetic disease [electronic resource] / Eamonn R. Maher. (ac.ke)
  • Huntington's disease (HD) is caused by expansion of polyglutamine repeats in the protein huntingtin, which affects the corpus striatum of the brain. (encyclopedia.pub)
IT152
  • In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. (uni-muenchen.de)
  • Lately, in 1993, gene IT15 (interesting transcript 15), which codes unstable protein huntingtin (htt) comprising variable number of CAG repeats, was identified [ 5 ]. (hindawi.com)
Genetic6
  • Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers. (geneticsmr.com)
  • One of the most common causes of genetic neurodegeneration is expansion of short repetitive DNA sequences, for example CAG trinucleotide repeats. (biologie-uni-siegen.de)
  • Mutations of the puratrophin-1 (PLEKHG4) gene on chromosome 16q22.1 are not a common genetic cause of cerebellar ataxia in a European population. (cdc.gov)
  • The presence of this genetic expansion results in an ataxin-3 protein containing a polyglutamine repeat region, which renders the ataxin-3 protein aggregation prone. (bvsalud.org)
  • CRISPRs are genetic elements containing direct repeats separated by unique spacers, many of which are identical to sequences found in phage and other foreign genetic elements. (berkeley.edu)
  • Genetic testing revealed 43 CAG repeats in the HD gene. (medscape.com)
Onset6
  • A higher number of CAG repeats is associated with an earlier age of onset. (arupconsult.com)
  • The number of repeats determines the risk and likely age of onset for symptom development. (arupconsult.com)
  • Mutant form of huntingtin (mhtt) comprises up to 40 repeats and individuals with 36-39 CAG repeats are in risk of developing adult (late-onset) form of HD. (hindawi.com)
  • Individuals with juvenile onset usually have over 55 repeats, and they usually inherit the gene from their father. (jci.org)
  • It is a triple nucleotide repeat, with age of onset correlating with the length of repeat. (medscape.com)
  • In all cases, age at onset correlates inversely with repeat number. (bmj.com)
Abnormal3
  • Many of the abnormal genes are of the expansion repeat variety. (medscape.com)
  • An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. (lookformedical.com)
  • 2] Healthy individuals may have between 9 and 35 CAG repeats, while patients diagnosed with HD, as well as carriers, have an abnormal expansion accommodating 36 or more CAG repeats. (medscape.com)
Mutations4
  • In addition to this there are some types of SCAs caused by other DNA mutations with other trinucleotide repeat expansion nucleotide repeats in non-coding regions of appropriate genes or non-repeat mutations and deletions. (ampkpathway.com)
  • We were interested to test if wild type huntingtin protected against the toxicity of polyglutamine expansion mutations. (bmj.com)
  • What this slide shows is that these types of mutations can occur in various parts of the gene. (hstalks.com)
  • The decision to rescreen a patient should be undertaken only with the guidance of a genetics professional who can best assess the incremental benefit of repeat testing for additional mutations. (acog.org)
Spinocerebellar2
  • Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). (nih.gov)
  • ataxias Spinocerebellar ataxias (SCAs) represent several intensifying hereditary neurodegenerative illnesses that change from one another in clinical demonstration and hereditary basis. (ampkpathway.com)
Brain4
  • Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. (uni-muenchen.de)
  • A basic difference between HD pathology in human and tgHD51 rats is in the rate of NDP progression that originates primarily from slow neuronal degeneration consequently resulting in lesser extent of concomitant reactive gliosis in the brain of tgHD51 rats. (hindawi.com)
  • We will study safety, in brain, of the molecules that initiate gene silencing. (grantome.com)
  • The scope is to evaluate if the new acquisitions may change the rehabilitation approaches to schizophrenia modifying the balance about the neurodevelopmental hypothesis of schizophrenia accepting that the cognitive deficits are produced by errors during the normal development of the brain (neurodevelopmental hypothesis) that remains stable in the course of illness and the neurodegenerative hypothesis according of which they derived from a degenerative process that goes on inexorably. (clinical-practice-and-epidemiology-in-mental-health.com)
Mutant4
  • Structurally, mutant CAG repeat RNA differs from the physiological RNA: the expanded CAG repeats fold into characteristic hairpin structures. (biologie-uni-siegen.de)
  • For example, we have identified a protein complex, which binds to and induces aberrant translation of mRNAs containing mutant CAG repeats. (biologie-uni-siegen.de)
  • We will examine how gene silencing can reduce production of the mutant huntingtin protein that causes HD, thereby preventing dysfunction and death in neurons in animal models of HD and in HD neurons in culture. (grantome.com)
  • The polyglutamine repeats in mutant huntingtin cause its aggregation and elicit toxicity by affecting several cellular processes, which include dysregulated organellar stress responses. (encyclopedia.pub)
Alleles5
  • The considered normal alleles have less than 27 CAG repeats. (geneticsmr.com)
  • Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. (geneticsmr.com)
  • Those with intermediate alleles are prone to this repeat instability and may have children with an HD-causing allele. (arupconsult.com)
  • Innovations include targeting mRNA alleles for RNAi, use of HD mouse models that express only human huntingtin genes, quantitative measurement of huntingtin allelic mRNA based on SNP heterozygosities, deep sequencing analysis to identify 3 UTR huntingtin mRNA regulation, and zinc finger nuclease strategy to eliminate huntingtin alleles at the genomic level. (grantome.com)
  • Those with a risk allele of rs903603 had an excess of apparent homozygosity for wild type repeat alleles, consistent with polymerase chain reaction failure of 1 allele because of massive repeat expansion. (ox.ac.uk)
Protein huntingtin1
  • it results from expansion of polyglutamine repeats in the protein huntingtin [ 1 ] . (encyclopedia.pub)
Chromosome3
  • For example, in OPCA-I (or SCA-1), the SCA1 gene is on chromosome 6. (medscape.com)
  • The SCA2 gene is on chromosome 12. (medscape.com)
  • But in a diseased chromosome, you might have 40 successive copies of CAG trinucleotides in the gene. (hstalks.com)
Instability2
  • Our results show that Msh2 is required for somatic instability of the CAG repeat. (nature.com)
  • Figure 3: Levels of CAG repeat instability in various tissues from Msh2 -/- , Msh2 +/- and Msh2 +/+ mice. (nature.com)
Wild-type huntingtin1
  • OBJECTIVES Recent data suggest that wild type huntingtin can protect against apoptosis in the testis of mice expressing full length huntingtin transgenes with expanded CAG repeats. (bmj.com)
Specific genes1
  • In any of the inherited cases, specific genes have been identified, although in most cases the precise way in which the genes exert a pathological influence is not known. (medscape.com)
Pathology1
  • With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation 11 , suggesting important functional correlations between repeat length and pathology. (nature.com)
Polyglutamine expansion1
  • RESULTS: We found that SH-SY5Y cells expressing human ataxin-3 containing polyglutamine expansion exhibited aberrant levels of autophagy substrates, including increased p62 and decreased LC3II (following bafilomycin treatment), compared to the controls. (bvsalud.org)
Triplet3
  • Such molecular defect is based on the expansion of this triplet that codes amino acid glutamine. (hindawi.com)
  • TTC triplet in the first intron of the FXN gene, encoding the essential mitochondrial protein frataxin. (frontiersin.org)
  • TTC triplet repeat expansion in an intron of the nuclear FXN gene, which encodes the essential mitochondrial protein frataxin ( 1 ). (frontiersin.org)
Glutamine1
  • The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. (wikipedia.org)
Neurotoxic1
  • In addition to encoding neurotoxic protein species, the CAG repeat RNA can have a toxic function itself. (biologie-uni-siegen.de)
Phenotypic1
  • It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. (nature.com)
Sperm1
  • However, large expansions of the CAG repeat region can occur during sperm formation. (arupconsult.com)
Individuals4
  • In unaffected individuals, there are 10-34 CAG repeats. (jci.org)
  • TTC repeats, whereas affected individuals have from approximately 70 to more than 1,000 triplets. (frontiersin.org)
  • Normal individuals have between 6 and 35 copies of this repeat. (upmc.com)
  • Affected individuals have an expanded repeat region, usually 36 to 121 copies of the repeat. (upmc.com)
Tissue2
  • Figure 1: Typical GeneScan traces for sizing of the CAG repeat from heart and striatal tissue of Msh2 -/- and Msh2 +/+ mice. (nature.com)
  • Treatment with cisplatin coupled with DHA might enhance cisplatin-induced expansion hang-up throughout SKOV3/DDP tissue. (pkcpathway.com)
Ataxia2
  • Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. (wikipedia.org)
  • Several such studies have indicated that such medications may produce modest improvement in ataxia caused by various neurodegenerative conditions, including OPCA. (medscape.com)
Occur1
Amyotrophic Lateral S1
  • Residual association at C9orf72 suggests an alternative amyotrophic lateral sclerosis-causing hexanucleotide repeat. (ox.ac.uk)
Sequence3
  • The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES). (wikipedia.org)
  • A BLAST analysis was used to suggest cross-reactivity with Human, Mouse, and Rat based on 100% sequence homology. (novusbio.com)
  • In this platform, catalytically inactive Cas9 serves as an RNA-guided DNA binding protein to silence gene expression in a sequence-specific manner. (berkeley.edu)
Specificity1
  • By interrogating microarray data from neuronal cells treated with inhibitors of different specificity, we selected two genes encoding histone macroH2A ( H2AFY2 ) and Polycomb group ring finger 2 ( PCGF2 ) that were specifically down-regulated by the inhibitors targeting HDACs1 and 3 versus the more selective inhibitors for further investigation. (frontiersin.org)
Genome3
  • Genome-wide association studies have identified a firm link between the human FTO gene, obesity and type II diabetes. (cmbn.no)
  • Although first observed in the 19th century, their structures were not identified until in the 1960s and their presence and fuller relevance in the human genome only clarified in the last few years. (anti-agingfirewalls.com)
  • R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome in- stability and regulated gene expression. (escholarship.org)
Amino2
  • Human HTT codes for a large protein of 3144 amino acids, which is ubiquitously expressed in various tissues and is present in several sub-cellular locations. (nature.com)
  • It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues. (lookformedical.com)
Mice1
  • Figure 2: Distribution of CAG repeats before and after the major GeneScan peak for various tissues from Msh2 -/- and Msh2 +/+ mice. (nature.com)
Methylation1
  • Methylation of mammalian DNA and histone residues are known to regulate transcription, and the discovery of demethylases that remove methylation in DNA and histones provide a basis for the understanding of dynamic regulation of mammalian gene expression. (cmbn.no)
Molecular Genetics1