Polyglutamine repeat humans gene contains trinucleotide repeat expansion. Medical search. Frequent questions

Regarding some SCAs molecular cloning strategies revealed the enlargement of CAG codons leading to lengthening of polyglutamine (polyQ) system in suitable proteins such as for example ataxins for SCA1 SCA2 SCA3 and SCA7 or α1A subunit of P/Q voltage-dependent calcium mineral channel (VDCC) Cav2.1 for SCA6 [2]. (ampkpathway.com)
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)
The cause of this fatal disease is an aberrant expansion of CAG trinucleotide in the exon 1 of HTT gene, translating into a polyglutamine tract (polyQ) at the N-terminus, and conferring gain-of-function and loss-of-function to wild type huntingtin protein. (biomedcentral.com)
For example in HD, the age of neurological onset is strongly associated with the length of polyglutamine (polyQ) expansion in huntingtin protein. (biomedcentral.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)
Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. (en-journal.org)

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)
While the experiments in the current paper were in progress, Leavitt et al 7 provided in vivo evidence suggesting that wild type huntingtin can protect against the gain of function mutation caused by the expanded polyglutamine tract in mutant huntingtin, using a YAC transgenic mouse model. (bmj.com)
This led us to propose that wild-type Ataxin-1 might take on a conformation that resists clearance or interacts strongly with other proteins and that such conformation is favored by the expanded polyglutamine tract. (bcm.edu)
The trinucleotide CAG codes for the amino acid glutamine and the expanded CAG repeats are translated into a series of uninterrupted glutamine residues (a polyglutamine tract). (ermateb.com)

Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. (nature.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)
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)
Worldwide, approximately 20% of cases of familial ALS are due to a mutation in the Cu/Zn superoxide dismutase-1 gene ( SOD1 ). (medscape.com)
METHOD: Mutation screening of positional candidate genes was performed in two stages. (neurotransmitter.net)

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)
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)

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)
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)
Variants (also called mutations) in the ATN1 gene can cause a very rare condition called congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA) syndrome. (medlineplus.gov)
We were interested to test if wild type huntingtin protected against the toxicity of polyglutamine expansion mutations. (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)
Mutations in the C9orf72 gene are responsible for 30-40% of familial ALS cases in the United States and Europe. (medscape.com)
We hypothesize that there might be at least three types of autism susceptibility genes/mutations that can be (i) specific to an individual patient or family, (ii) in a genetically isolated sub-population and (iii) a common factor shared amongst different populations. (neurotransmitter.net)
The genes/mutations could act alone or interact with other genetic and/or epigenetic or environmental factors, causing autism or related disorders. (neurotransmitter.net)

Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. (cdc.gov)
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)
Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. (nature.com)
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)
Huntington's disease (HD) is the most prevalent autosomal dominant, trinucleotide repeat neurodegenerative 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)
Evidence for DNA repair genes modifying Huntington's disease has been mounting for years. (ermateb.com)
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)

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)
2014). Although this study aims to find therapeutic benefit through nonallele-specific silencing of both the mutant and wild type huntingtin gene which codes for the huntingtin protein, it has been noted that the effects of nonallelle-specific silencing of the mutant htt still remains unknown. (edubirdie.com)

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)
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)

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)

In this study researchers used human cells and techniques that can read DNA repeat expansions, the researchers found that FAN1 can block the accumulation of the DNA mismatch repair factors to stop repeat expansion thus alleviating toxicity in cells derived from patients. (ermateb.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)
To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model. (biomedcentral.com)

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)
The length of the extended polyglutamine stretches in the corresponding proteins is proportionally related to their aggregation propensity. (nih.gov)
iPSC generation and neuronal differentiation are unaffected by polyglutamine proteins and show no spontaneous aggregate formation. (nih.gov)
A transcriptional co-repressor is a protein that interacts with other DNA-binding proteins to suppress the activity of certain genes, although it cannot attach (bind) to DNA by itself. (medlineplus.gov)
The extended CAG region changes the structure of atrophin 1 and how the protein interacts with other proteins to control gene function. (medlineplus.gov)
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)

Human Molecular Genetics. (wikipedia.org)
American Journal of Human Genetics. (wikipedia.org)
Journal of human genetics 2006 51 (4): 363-7. (cdc.gov)

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)
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)
These diseases relate to wide group of polyglutamine disorders. (ampkpathway.com)
Andrew, S.E., Goldberg, Y.P. & Hayden, M.R. Rethinking genotype and phenotype correlations in polyglutamine expansion disorders. (nature.com)

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). (bvsalud.org)
Many of the abnormal genes are of the expansion repeat variety. (medscape.com)

A cytidine, thymidine, guanosine (CTG) trinucleotide repeat expansion that is incorporated into the SCA8 but not the KLHL1 transcript causes spinocerebellar ataxia type 8. (wikipedia.org)
GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 8 Human ATXN8OS genome location and ATXN8OS gene details page in the UCSC Genome Browser. (wikipedia.org)
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)
Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). (nih.gov)

Upregulation of DNAJB6 in neurons antagonizes glutamate-induced aggregation, while knockdown of DNAJB6 in progenitors results in spontaneous polyglutamine aggregation. (nih.gov)
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)

It is a triple nucleotide repeat, with age of onset correlating with the length of repeat. (medscape.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)
Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). (neurotransmitter.net)

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)
First, these approaches are designed to identify individual modifier genes with strong phenotypic effects. (biomedcentral.com)

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)

CAG-repeat expansions in at least eight different genes cause neurodegeneration. (nih.gov)
At the moment about 30 different genes have already been identified which may be the reason for these illnesses [1]. (ampkpathway.com)

The ATN1 gene variants that cause CHEDDA syndrome occur in one of the two copies of the gene in each cell and lead to a change in single protein building blocks (amino acids) in atrophin 1. (medlineplus.gov)
Such molecular defect is based on the expansion of this triplet that codes amino acid glutamine. (hindawi.com)
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)
These mice express the human htt cDNA which encodes glutamine and the first 171 amino acids bearing 82 CAG repeats (Schilling et al. (edubirdie.com)

The normal number of CAG repeats is 10-35 times, however, in HD this repeat will occur 36 times or more and as CAG codes for glutamine, HD is classified as a polyglutamine disease. (edubirdie.com)

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)
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)
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)
However, how lncRNAs contribute to the development of hereditary diseases in human is still mostly unknown. (biomedcentral.com)

Genome-wide association studies have identified a firm link between the human FTO gene, obesity and type II diabetes. (cmbn.no)
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)
Thousands of long non-coding RNA (lncRNA) genes are annotated in the human genome. (biomedcentral.com)
1996) by inserting a part of the htt gene from a juvenile HD patient into the mouse genome. (edubirdie.com)
R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome in- stability and regulated gene expression. (escholarship.org)

Using a newly developed human neuronal cell model, derived from patient-induced pluripotent stem cells, we find that 2-aminobenzamide histone deacetylase (HDAC) inhibitors increase FXN mRNA levels and frataxin protein in FRDA neuronal cells. (frontiersin.org)
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)

Chaudhry A, Anthanasiou-Fragkouli A, Houlden H. DRPLA: understanding the natural history and developing biomarkers to accelerate therapeutic trials in a globally rare repeat expansion disorder. (medlineplus.gov)
Nagafuchi S, Yanagisawa H, Ohsaki E, Shirayama T, Tadokoro K, Inoue T, Yamada M. Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA). (medlineplus.gov)
It is classed as a trinucleotide repeat disorder (Marcy et al, 1993) due to the fact that it results from an expanded CAG repeat which leads to a polyglutamine strand of variable length at the N-terminus (Walker, 2007). (edubirdie.com)

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)

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)

The huntingtin gene which regulates brain-derived neurotrophic factor (BDNF) that promotes the survival of neurons in the brain is affected (Zuccato et al, 2010). (edubirdie.com)
The loss of small neurons will also cause the expansion of the lateral ventricles and this can lead to psychological problems such as dementia, personality changes and depression. (edubirdie.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)

The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. (neurotransmitter.net)
Yet age of onset can vary by several decades in people carrying the same length polyglutamine expansion, and a large proportion of this residual variation is genetic in nature and may be due to polymorphisms in other genes [ 12 - 15 ]. (biomedcentral.com)

Transcriptional dysregulation is considered a key molecular mechanism responsible of HD pathogenesis but, although numerous studies investigated mRNA alterations in HD, so far none evaluated a whole gene expression profile in blood of R6/2 mouse model. (biomedcentral.com)

Presumably the expansion interferes with normal antisense function of this transcript. (wikipedia.org)

Figure 1: Typical GeneScan traces for sizing of the CAG repeat from heart and striatal tissue of Msh2 -/- and Msh2 +/+ mice. (nature.com)
Figure 2: Distribution of CAG repeats before and after the major GeneScan peak for various tissues from Msh2 -/- and Msh2 +/+ mice. (nature.com)
On the other hand, MALAT1 whose sequence is highly conserved between human and mice do not tend to be conserved on the functional level. (biomedcentral.com)
Knockdown experiments on human and mice lung cancer cell lines showed a decrease migration and metastatic rate in human. (biomedcentral.com)
Knock in mice models have more precise portrayal of the disease`s genotype as scientists are able to replace specific gene regions of the HD gene with human copies. (edubirdie.com)
The purpose of these mice was to be able to study and understand repeat expansion which leads to Huntington`s Disease. (edubirdie.com)

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. (nature.com)
We will study safety, in brain, of the molecules that initiate gene silencing. (grantome.com)
Selected genes derived from these pathways were additionally investigated in other accessible tissues to validate these matrices as source of biomarkers, and in brain, to link central and peripheral disease manifestations. (biomedcentral.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)

In unaffected individuals, there are 10-34 CAG repeats. (jci.org)
Individuals with juvenile onset usually have over 55 repeats, and they usually inherit the gene from their father. (jci.org)
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)
TTC repeats, whereas affected individuals have from approximately 70 to more than 1,000 triplets. (frontiersin.org)

In this study, we used peripheral blood mononuclear cells (PBMCs) from a volunteer with 14/63 CAG repeats in ATXN3 to generate induced pluripotent stem cells (iPSCs), which will be a good model for studying SCA3. (bvsalud.org)

The age of onset of the disease varies inversely with the number of CAG repeats. (jci.org)
The level of the polyglutamine-expanded protein is one of the factors that contributes to disease severity. (nih.gov)
This proposal addresses treatment of HD through study of basic mechanisms of silencing the gene that causes the disease. (grantome.com)
The disease is caused by an increased CAG repeat number in a gene coding for a protein with an unknown function, called huntingtin. (ermateb.com)

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)

When the CTG expansion is present, a polyglutamine mutant protein is produced. (wikipedia.org)

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)

In all cases, age at onset correlates inversely with repeat number. (bmj.com)

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)

Both genes are involved in transcriptional repression and we speculate their involvement in FXN gene silencing. (frontiersin.org)

It had been demonstrated that the increased loss of Mirabegron CB and PV results in the modifications in Cav2.1 stations (P/Q-type VDCCs) encoded by gene [14]. (ampkpathway.com)
DRPLA results from an increased number of copies (expansion) of the CAG trinucleotide repeat in the ATN1 gene. (medlineplus.gov)
it results from expansion of polyglutamine repeats in the protein huntingtin [ 1 ] . (encyclopedia.pub)

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)
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)

Ataxin 8 opposite strand, also known as ATXN8OS, is a human gene. (wikipedia.org)

Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. (neurotransmitter.net)

Anatomy6

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Psychiatry and Psychology2

Phenomena and Processes32

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Health Care1

PolyQ6

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Exon5

Mutations8

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Huntingtin protein2

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Wild-type huntingtin1

Toxicity3

Proteins8

Genetics3

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IT151

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