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 ProteinsAllelesMutationRepetitive Sequences, Nucleic AcidCytoplasmBase SequenceSpinocerebellar AtaxiasMolecular Sequence DataMachado-Joseph DiseaseHeredodegenerative Disorders, Nervous SystemNerve Tissue ProteinsDNAGenomic InstabilityFrontotemporal DementiaFlap EndonucleasesMicrosatellite RepeatsAnticipation, GeneticNucleic Acid ConformationInverted Repeat SequencesPedigreeTandem Repeat SequencesMinisatellite RepeatsAge of OnsetCerebellar AtaxiaPolymerase Chain ReactionIntranuclear Inclusion BodiesRNA-Binding ProteinsChromosome FragilityMuscular Dystrophy, OculopharyngealGenetic Diseases, InbornNuclear ProteinsPolymorphism, GeneticAmyotrophic Lateral SclerosisAmino Acid SequencePhenotypeSequence Analysis, DNANeurodegenerative DiseasesProteinsTranscription, GeneticPeptidesRNA, MessengerDNA RepairDNA PrimersMice, TransgenicModels, GeneticReceptors, AndrogenGenotypeDNA-Binding ProteinsSaccharomyces cerevisiaeExonsGenes, DominantDNA ReplicationCell LineGenome, HumanHeterozygoteMyoclonic Epilepsies, ProgressiveRepetitive Sequences, Amino AcidGenetic MarkersGenetic VariationMutS Homolog 2 ProteinSaccharomyces cerevisiae ProteinsDisease Models, AnimalNucleic Acid HeteroduplexesRNAGene FrequencyPromoter Regions, GeneticChromosome MappingCell Nucleus
NucleusNeuronsExonMutationsEncodesHuntingtin geneIT15TranscriptAbnormalOnsetAggregatesExonsUnstableDisorderC9ORF72Autosomal dominantMRNASOD1Amino acidsMutantBackboneProcessesAccumulatesToxicDiseasesIndividualsThought to occurBrainsNucleotidesSequencesTranscriptionalIncreasesDisordersTripletEmbryogenesisGeneticChromosomeMolecularSpecificExpressionFormAcuteDiseaseFamilialHumanLethalFunctionPotentialBody
Nucleus5
  • One theory is that accumulation of RNA in the nucleus and cytoplasm becomes toxic, and RNA binding protein sequestration occurs. (wikipedia.org)
  • Western blot analysis of HD brain tissue shows full-length huntingtin protein in the nuclear fraction as well as abundant immunopositive bands at lower molecular weight, suggesting proteolytic products in the nucleus. (jci.org)
  • 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)
  • Then it leaves the nucleus and forms protein at the ribosome using the help of tRNA and rRNA. (geneticeducation.co.in)
  • So before leaving the nucleus, the gene sheds off introns from the mRNA and moves to the ribosome so the introns remain in the nucleus only and don't translate while the exons move out of the nucleus, to the cytoplasm and do the translation. (geneticeducation.co.in)
Neurons2
  • The protein is found in many regions of the brain, in the cytoplasm of neurons as well as in presynaptic terminals. (wikipedia.org)
  • HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans . (en-journal.org)
Exon6
  • Exon 1 contains a CAG trinucleotide repeat that encodes the amino acid glutamine, followed by another repeat that encodes proline. (jci.org)
  • 35) in the first exon of the huntingtin ( HTT , IT15 ) gene 1 . (nature.com)
  • Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). (en-journal.org)
  • Exon and introns are the nucleic acid sequence made up of the polynucleotide chain. (geneticeducation.co.in)
  • The exon makes proteins while the intron regulates gene expression. (geneticeducation.co.in)
  • The final product of the exon is protein hence it is present in DNA as well as mRNA which means it is present during all DNA metabolic actions like replication, transcription and translation. (geneticeducation.co.in)
Mutations5
  • Disease-causing mutations in the gene were first discovered by two independent research teams, led by Rosa Rademakers of Mayo Clinic and Bryan Traynor of the National Institutes of Health, and were first reported in October 2011. (wikipedia.org)
  • While different mutations of various genes have been linked to different phenotypes of FTD in the past, C9orf72 specifically has been linked to behavioral variant FTD. (wikipedia.org)
  • In humans, mutations affecting the genes of this family are associated with specific diseases. (sdbonline.org)
  • other mutations involving the FMR1 gene can cause FXS if they prevent production or alter functional domains of the encoded protein, the fragile X mental retardation protein (FMRP) ( O'Donnell and Warren, 2002 ). (jneurosci.org)
  • Mutations in the C9orf72 gene are responsible for 30-40% of familial ALS cases in the United States and Europe. (medscape.com)
Encodes2
  • The lilli gene encodes a nuclear protein related to the AF4/FMR2 family. (sdbonline.org)
  • The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
Huntingtin gene1
  • Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. (nature.com)
IT151
  • 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)
Transcript2
  • Almost half of the genes expressed in adults showed reduced expression, supporting a broad role for the three tested genes in steady-state transcript abundance. (sdbonline.org)
  • As we said above the introns and exons are located one after another in a gene to make a transcript, introns must be removed first. (geneticeducation.co.in)
Abnormal4
  • Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). (bvsalud.org)
  • proteinopathic adj ), or proteopathy , protein conformational disorder , or protein misfolding disease , is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells , tissues and organs of the body. (wikipedia.org)
  • For example, proteins that are normally unfolded or relatively unstable as monomers (that is, as single, unbound protein molecules) are more likely to misfold into an abnormal conformation. (wikipedia.org)
  • The abnormal aggregation and accumulation of specific proteins in the form of cytoplasmic inclusion is common pathological feature of most age-related neurodegenerative diseases, such as Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD) and amyotrophic lateral sclerosis (ALS). (en-journal.org)
Onset5
  • However, only 1 in 4 families exhibited significant anticipation in this study (n=63) It has been proposed that the amount of the repeat expansion increases with each successive generation, possibly causing the disease to be more severe in the next generation, showing onset up to a decade earlier with each successive generation after the carrier. (wikipedia.org)
  • The age of onset of the disease varies inversely with the number of CAG repeats. (jci.org)
  • Individuals with juvenile onset usually have over 55 repeats, and they usually inherit the gene from their father. (jci.org)
  • 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)
  • 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)
Aggregates1
  • [10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. (wikipedia.org)
Exons7
Unstable1
  • The buildup of a repeat expansion with each generation is typically thought to occur because the DNA is unstable and therefore accumulates exponentially every time the gene is copied. (wikipedia.org)
Disorder1
  • This hexanucleotide variant of a trinucleotide repeat disorder produces five different dipeptides by RAN translation, these dipeptides aggregating to contribute to overall toxicity of the mutation. (wikipedia.org)
C9ORF7210
  • C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene C9orf72. (wikipedia.org)
  • The human C9orf72 gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,546 to base pair 27,573,866 (GRCh38). (wikipedia.org)
  • Cytogenetic Location: 9p21.2 Molecular Location on chromosome 9: base pairs 27,546,546 to 27,573,866 The mutation of C9ORF72 is a hexanucleotide repeat expansion of the six letter string of nucleotides GGGGCC. (wikipedia.org)
  • It is known that the mutation interferes with normal expression of the protein made by C9orf72, however the function of this protein remains speculative. (wikipedia.org)
  • The other is that the lack of half of the C9ORF72 protein (haploinsufficiency) in the body causes the diseases. (wikipedia.org)
  • Additionally, RNA transcribed from the C9ORF72 gene, containing expanded GGGGCC repeats, is translated through a non-ATG initiated mechanism, which is the same mechanism as other repeat disorders. (wikipedia.org)
  • The GGGGCC repeat expansion in C9orf72 is also believed to compromise nucleocytoplasmic transport through several possible mechanisms. (wikipedia.org)
  • Numerous published studies have confirmed the commonality of the C9ORF72 repeat expansion in FTD and ALS, which are both diseases without cures that have affected millions of people. (wikipedia.org)
  • Certain pathology in FTD caused by the C9orf72 mutation can also include: TDP-43 in all C9 carriers Ubiquitin-binding protein 62 C9ORF72 is specifically linked to familial ALS, which affects about 10% of ALS patients. (wikipedia.org)
  • Possibly most importantly, the identification of this hexanucleotide repeat expansion is an extremely promising avenue for possible future therapies of both familial FTD and familial ALS, once the mechanism and function of the C9ORF72 protein is better comprehended. (wikipedia.org)
Autosomal dominant1
  • Genetically, HSPs are classified by the mode of inheritance (autosomal dominant, autosomal recessive, and X-linked) and are subdivided by chromosomal locus or causative gene. (medscape.com)
MRNA4
  • The mRNA and protein levels of ATXN3 was evaluated in pancreatic cancer samples and cell lines. (bvsalud.org)
  • Technically speaking, a gene is a polynucleotide chain of DNA that makes a protein via mRNA. (geneticeducation.co.in)
  • After replication, the entire DNA is copied and makes mRNA via transcription. (geneticeducation.co.in)
  • The mRNA is a type of ribonucleic acid that has uracil instead of thymine in it and contains the genetic information to make protein. (geneticeducation.co.in)
SOD11
  • Worldwide, approximately 20% of cases of familial ALS are due to a mutation in the Cu/Zn superoxide dismutase-1 gene ( SOD1 ). (medscape.com)
Amino acids1
  • 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)
Mutant1
  • These mutant phenotypes correlate with markedly reduced expression of the early zygotic genes serendipity alpha , fushi tarazu and huckebein , which are essential for cellularization and embryonic patterning (Tang, 2001). (sdbonline.org)
Backbone2
  • The process constructs Three dimensional fencing that will independent nearby backbone via valley-emphasized Gaussian photographs. (pkcpathway.com)
  • [13] [14] Because proteins share a common structural feature known as the polypeptide backbone, all proteins have the potential to misfold under some circumstances. (wikipedia.org)
Processes2
  • 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)
  • In the central dogma RNA acts as a simple intermediary between the DNA that carries the genetic information and the proteins that define the whole variety of biological processes in the cell. (biomedcentral.com)
Accumulates1
  • Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease , immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy . (wikipedia.org)
Toxic1
  • in this misfolded state, the proteins can become toxic in some way (a toxic gain-of-function ) or they can lose their normal function. (wikipedia.org)
Diseases1
  • Testing for a specific gene that is known to cause the diseases would help with faster diagnoses. (wikipedia.org)
Individuals1
  • In unaffected individuals, there are 10-34 CAG repeats. (jci.org)
Thought to occur1
Brains1
  • [9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. (wikipedia.org)
Nucleotides1
  • The promoters are leading nucleotides that help a gene to form a protein like a signal entry gate that allows various enzymes to take part in the protein formation. (geneticeducation.co.in)
Sequences2
  • Large international consortiums such as ENCODE (The Encyclopedia of DNA Elements) has shown that up to 80% of the genome is transcribed while only 1,5% of it is protein -coding sequences [ 1 ]. (biomedcentral.com)
  • While the introns that are often known as intervening sequences regulate gene expression. (geneticeducation.co.in)
Transcriptional1
  • These results suggest that transcriptional elongation control is especially important for rapidly expressed genes to support digestion and metabolism, many of which have sex-biased function. (sdbonline.org)
Increases2
  • In most, if not all proteinopathies, a change in the 3-dimensional folding conformation increases the tendency of a specific protein to bind to itself. (wikipedia.org)
  • Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. (en-journal.org)
Disorders1
  • [15] However, only a relatively small number of proteins are linked to proteopathic disorders, possibly due to structural idiosyncrasies of the vulnerable proteins. (wikipedia.org)
Triplet2
  • Such molecular defect is based on the expansion of this triplet that codes amino acid glutamine. (hindawi.com)
  • Each DNA sequencing has a specific triplet code known as genetic code that makes an amino acid. (geneticeducation.co.in)
Embryogenesis1
  • lilli functions as a maternally provided pair-rule gene that is essential for proper cellularization, gastrulation and segmentation during embryogenesis. (sdbonline.org)
Genetic1
  • Spinocerebellar ataxia type 3 (SCA3) is a genetic degeneration disease of the nervous system with ataxia as the main clinical manifestation, and the most frequent subtype of SCA3 is known to be caused by CAG repeat expansions of more than 55 units in ATXN3. (bvsalud.org)
Chromosome1
Molecular1
  • 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)
Specific1
  • According to the GENCODE project one third of all human lncRNAs genes are primate-specific [ 4 ]. (biomedcentral.com)
Expression4
  • Genes showing reduced expression due to these RNAi treatments were short and enriched for genes encoding metabolic or enzymatic functions. (sdbonline.org)
  • Hundreds of genes were observed with sex-biased differential expression following treatment. (sdbonline.org)
  • We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
  • Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)
Form3
  • [9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross- polarized light after staining with the dye Congo red , as well as a fibrillar ultrastructure when viewed with an electron microscope . (wikipedia.org)
  • [5] In this aggregated form, the protein is resistant to clearance and can interfere with the normal capacity of the affected organs. (wikipedia.org)
  • While the introns are included in the non-coding junk portion of a genome which can't form protein but do something else. (geneticeducation.co.in)
Acute1
  • Translocations between MLL (a human trithorax -related gene) and AF4 or AF5q31 are involved in acute lymphoblastic leukemia (Wittwer, 2001, Tang, 2001 and Su, 2001). (sdbonline.org)
Disease1
  • [20] They have been most thoroughly studied with regard to prion disease , and are referred to as protein strains . (wikipedia.org)
Familial2
  • Traditionally, familial and sporadic cases of ALS have been clinically indistinguishable, which has made diagnosis difficult. (wikipedia.org)
  • The identification of this gene will therefore help in the future diagnosis of familial ALS. (wikipedia.org)
Human2
  • Ataxin-3 (ATXN3) protein is a deubiquitinating enzyme implicated in the occurrence of diverse human cancers. (bvsalud.org)
  • Thousands of long non-coding RNA (lncRNA) genes are annotated in the human genome. (biomedcentral.com)
Lethal1
  • 2) lilli mutation strongly suppresses the rough eye phenotype of ectopically expressed phyllopod (Tang, 2001), and (3) lilli was identified in a screen for genes that enhance the embryonic lethal phenotype of dpp alleles (Su, 2001). (sdbonline.org)
Function3
  • Huntingtin contains a few domains that suggest particular functions, including WW domains and caspase cleavage sites ( 7 , 8 ), but the function of the protein remains unknown. (jci.org)
  • Synaptic function and plasticity were studied in mice lacking the fragile X mental retardation protein (FMRP), a model for the fragile X mental retardation syndrome. (jneurosci.org)
  • In some cases, misfolding of the protein results in a loss of its usual function. (wikipedia.org)
Potential1
  • We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). (nature.com)
Body1