RepeatsGenome instabilityChromosomeGeneHuntington'sExpansionsExpansionGait instabilityPostural instabilitySomaticMutationSequenceAmino acidAllelesHumanPreventsUnstableMiceIncreaseGenomic instabilityMicrosatellite instabilityGenome InstabilityIntergenerationalGeneticMeioticRepeat disordersONSETReplicationSequencesProgressionSize
Repeats15
- The number of trinucleotide repeats appears to predict the progression, severity, and age of onset of Huntington's disease and similar trinucleotide repeat disorders. (wikipedia.org)
- because of this, it took almost 200 years for a link between onset of disease and trinucleotide repeats (TNR) to be acknowledged. (wikipedia.org)
- Trinucleotide repeats are a source of genome instability, causing replication fork stalling, chromosome fragility, and impaired repair. (tufts.edu)
- 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)
- Instability of highly expanded CAG repeats in mice transgenic for the Huntington's disease mutation. (nature.com)
- Regions of repetitive DNA, in particular trinucleotide repeats, are common throughout the human genome and are of interest as a source of genomic instability. (brown.edu)
- Sequencing of their polymerase chain reaction (PCR) products revealed a G-->A transition immediately preceding the trinucleotide repeats, hence defining 8 distinct haplotypes and 36 possible genotypes. (scite.ai)
- Huntington disease (HD) is caused by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats within the HTT gene. (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)
- Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. (edu.sa)
- We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. (edu.sa)
- 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)
- The most common SCA are characterized by expanded CAG trinucleotide that repeats the encode glutamine amino acid, the so-called polyglutamine diseases. (scielo.br)
- Garribba L, Vogel I, Lerdrup M, Goncalves Dinis MM, Ren L and Liu Y . Folate Deficiency Triggers the Abnormal Segregation of a Region With Large Cluster of CG-Rich Trinucleotide Repeats on Human Chromosome 2. (ku.dk)
- A fascinating example of enhanced cell-type-specific disease vulnerability is seen in Huntington's disease (HD), a monogenic neurodegenerative disease caused by expansion of CAG (glutamine-encoding) trinucleotide repeats in the huntingtin gene. (mit.edu)
Genome instability5
- In addition to gene expression, mutational signatures-readouts of genome instability-can characterize DNA repair deficiencies. (nature.com)
- Our research focus is to understand the structure and function of unusual DNA sequences in living cells, and how these sequences cause genome instability and lead to human diseases. (virginia.edu)
- Genome Instability & Disease, 2020. (ku.dk)
- However, they can also induce detrimental genome instability and numerous human diseases ( 3 , 6 ). (rna-mediated.com)
- Mechanisms of Genome Instability in the Fragile X-Related Disorders. (cdc.gov)
Chromosome4
- Myotonic dystrophy is nucleotide repeat expansion disorder in which type 1 (DM1) is due to a trinucleotide repeat expansion on chromosome 19 and type 2 (DM2) arises from a tetranucleotide repeat expansion on chromosome 3. (jci.org)
- But in a diseased chromosome, you might have 40 successive copies of CAG trinucleotides in the gene. (hstalks.com)
- HD arises from a CAG trinucleotide repeat expansion on chromosome 4 . (sketchy.com)
- 2006). A novel trinucleotide repeat expansion at chromosome 3q26.2 identified by a CAG/CTG repeat expansion detection array . (up.pt)
Gene7
- 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)
- Fragile X syndrome (FXS) is caused by expansion of the CGG trinucleotide repeat in the Fragile X Mental Retardation gene, FMR1 . (ny.gov)
- Trinucleotide repeat expansion in the FMR1 gene is caused by instability in early development and during germ cell production and is thought to be a result of DNA polymerase slippage during DNA replication. (ny.gov)
- A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. (nature.com)
- The gene defect is caused by instability of the FMRI gene region. (reprosource.com)
- We are also interested in the nature of trinucleotide repeat expansion diseases, in which an expanded trinucleotide repeat block is present in a gene for which loss or alteration leads to the disease. (virginia.edu)
- Molecular research included specific gene sequencing, trinucleotide enlargement characterization, fresh generation multigene sequencing and entire genome and exome sequencing. (unambitiousus.com)
Huntington's2
- Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. (nature.com)
- Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. (nature.com)
Expansions5
- Long expansions of transcribed trinucleotide microsatellites have been etiologically associated with some neurological diseases. (scite.ai)
- Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1 protein levels play an important role in driving of the efficiency of somatic expansions. (elsevierpure.com)
- Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. (edu.sa)
- Developing representative models of myotonic dystrophy in animals has been challenging due to instability of nucleotide repeat expansions, especially for DM2 which is characterized by nucleotide repeat expansions often greater than 5000 copies. (jci.org)
- Today I'm going to tell you about microsatellites, and trinucleotide repeat expansions diseases. (hstalks.com)
Expansion7
- A trinucleotide repeat expansion, also known as a triplet repeat expansion, is the DNA mutation responsible for causing any type of disorder categorized as a trinucleotide repeat disorder. (wikipedia.org)
- In addition to occurring during DNA replication, trinucleotide repeat expansion can also occur during DNA repair. (wikipedia.org)
- Each of these processes involves a DNA synthesis step in which strand slippage might occur leading to trinucleotide repeat expansion. (wikipedia.org)
- This is the first study to examine FXS and trinucleotide repeat expansion in human embryonic stem cells. (ny.gov)
- Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. (elsevierpure.com)
- HD also displays anticipation , a phenomenon where subsequent generations manifest the disease at an earlier age and with increased severity due to the expansion of the trinucleotide repeat. (sketchy.com)
- Beyond Trinucleotide Repeat Expansion in Fragile X Syndrome: Rare Coding and Noncoding Variants in FMR1 and Associated Phenotypes. (cdc.gov)
Gait instability2
- The predominant sign at onset was gait instability and falls. (unambitiousus.com)
- Approximately 15% of patients follow a primary progressive or progressive relapsing course from disease onset, usually characterized by symptoms of progressive myelopathy (gait instability, spasticity, bladder symptoms) and cognitive impairment. (medscape.com)
Postural instability2
- and a shuffling gait, a consequence of the combined effects of bradykinesia and postural instability. (sketchy.com)
- Specifically, the motor symptoms of Parkinson's disease (PD) - including resting tremor, rigidity, akinesia, and postural instability - are seen upon dopamine depletion in the brain, resultant from the death of dopamine-producing cells in the substantia nigra. (mit.edu)
Somatic3
- One common type of signature describes relative frequencies of somatic single-nucleotide variants (SNV) across different trinucleotide contexts. (nature.com)
- Our results show that Msh2 is required for somatic instability of the CAG repeat. (nature.com)
- 2005). Haplotype diversity and somatic instability in normal and expanded SCA8 alleles . (up.pt)
Mutation1
- Indeed, mutation detection enhancement gel electrophoresis of mixed PCR products from cloned haplotypes revealed 24 distinct heteroduplex patterns for the six possible trinucleotide heterozygotes. (scite.ai)
Sequence3
- When a DNA trinucleotide repeat sequence is damaged, it may be repaired by processes such as homologous recombination, non-homologous end joining, mismatch repair or base excision repair. (wikipedia.org)
- Prof. Brahmachari has made major contributions in molecular analysis of genetic disorders associated with trinucleotide amplification and repetitive sequence instability. (rnabiology.org)
- We searched the expressed sequence tag databank for reiterated trinucleotides and selected EST00493 (D2S196E) with 14 tandem ACA triplets as a potentially polymorphic locus. (scite.ai)
Amino acid1
- Exon 1 contains a CAG trinucleotide repeat that encodes the amino acid glutamine, followed by another repeat that encodes proline. (jci.org)
Alleles1
- Those with intermediate alleles are prone to this repeat instability and may have children with an HD-causing allele. (arupconsult.com)
Human1
- Hsp90 modulates CAG repeat instability in human cells. (bcm.edu)
Prevents1
Unstable1
- We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. (edu.sa)
Mice1
- Figure 3: Levels of CAG repeat instability in various tissues from Msh2 -/- , Msh2 +/- and Msh2 +/+ mice. (nature.com)
Increase1
- Inhibition of the recombinase Rad51, a downstream target of Hsp90, induces a comparable increase in repeat instability, suggesting that Hsp90-enabled homologous recombination normally functions to stabilize CAG repeat tracts. (bcm.edu)
Genomic instability4
- BRCA1 and BRCA2 are repair enzymes involved in double-stranded DNA break repair, and mutations in these genes lead to genomic instability and increased rates of variation and are associated with a high risk of developing breast, ovarian, and fallopian tube cancers (Genetics of Breast Cancer: A Topic in Evolution, Annals of Oncology 26:1291, 2015). (stratech.co.uk)
- Structural alterations in DNA can serve as natural impediments to replication fork stability and progression, resulting in DNA damage and genomic instability. (researchensemble.com)
- In the absence of XPA or XPC, TR-701 deleterious effects of triplex-induced genomic instability may become averted by activating apoptosis via dual phosphorylation of the H2AX protein. (researchensemble.com)
- Conditions that alter replication shell structure during DNA synthesis can perfect the region for chromosomal breakage, therefore becoming a major resource of spontaneous genomic instability, and as a result traveling malignant change of pre-cancerous cells. (researchensemble.com)
Microsatellite instability1
- The assay detects single nucleotide variants (SNV), indels, focal copy number alterations (CNA), TERT promoter region, as well as tumor mutation burden (TMB) and microsatellite instability (MSI) status. (oncotarget.com)
Genome Instability1
- Mechanisms of Genome Instability in the Fragile X-Related Disorders. (cdc.gov)
Intergenerational1
- Anticipation and intergenerational repeat instability in spinocerebellar ataxia type 17. (medlineplus.gov)
Genetic3
- The instability of the CAG repeat size of the HD gene when transmitted intergenerationally has critical implications for genetic counseling practices. (tau.ac.il)
- Improving our knowledge of the entire repeat sequence will help us make clearer correlations between the genetic instability and the clinical manifestations of DM1. (pacb.com)
- Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. (org.ua)
Meiotic1
- Potter NT , Meiotic instability associated with the CAGR1 trinucleotide repeat at 13q13. (coriell.org)
Repeat disorders1
ONSET1
- Our results suggest POLG CAG repeat instability would constitute a predisposing factor that, in combination with environmental risk factors, affect age of onset and disease progression. (nih.gov)
Replication1
Sequences1
- 31 Therefore, we have hypothesised that mutagenic stress could result in an induction of instability of unexpanded TNR sequences, leading to an increase in the frequency of spontaneously occurring contractions/expansions in repeat number. (bmj.com)
Progression1
- With disease progression, chorea coexists with and gradually is replaced by dystonia and parkinsonian features, such as bradykinesia, rigidity, and postural instability. (medscape.com)
Size1
- If the disorder is characterized by long lengths of trinucleotides gone haywire, then it would be advantageous to be able to shrink the repeat regions back down to an asymptomatic size. (pacb.com)