• Here, two patients with bvFTD-SP with chromosome 9 open reading frame 72 (C9ORF72) hexanucleotide expansions are described. (bmj.com)
  • Methods 384 patients with an FTD clinical spectrum and Alzheimer's disease diagnoses were screened for C9ORF72 expansion. (bmj.com)
  • Large expansions of a non-coding GGGGCC-repeat in the first intron of the C9orf72 gene are a common cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). (nature.com)
  • Here we show using NMR and CD spectroscopy that the C9orf72 hexanucleotide expansion can form a stable G-quadruplex, which has profound implications for disease mechanism in ALS and FTD. (nature.com)
  • Large expansions of the non-coding GGGGCC-repeat in the first intron of the C9orf72 gene have been recently demonstrated to cause ALS and FTD 5 , 6 . (nature.com)
  • The GGGGCC expansion of C9orf72 forms runs of adjacent G-repeats and raises the possibility these could form G-quadruplexes. (nature.com)
  • Repeat expansion mutations in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). (frontiersin.org)
  • 2011) identified a polymorphic hexanucleotide repeat (GGGGCC) located between the noncoding exons 1a and 1b of the C9ORF72 gene. (coriell.org)
  • The expanded repeat is located in the promoter region of C9ORF72 transcript variant 1 and in intron 1 of transcript variants 2 and 3. (coriell.org)
  • A polymerase chain reaction-based assay is utilized to detect C9orf72 GGGGCC hexanucleotide repeat expansions. (mayocliniclabs.com)
  • First tier testing for a diagnosis of dementia or amyotrophic lateral sclerosis is C9ORF / C9orf72 , Hexanucleotide Repeat, Molecular Analysis, Varies, which is included with this test but is also available separately. (mayocliniclabs.com)
  • The introns containing these large expansions are transcribed and indeed in patients the GGGGCC-repeat expansion is detectable by in situ hybridization in nuclear RNA foci 5 . (nature.com)
  • Overall, 75 (10.4%) of 722 unrelated patients with FTD, ALS, or both were found to carry an expanded GGGGCC repeat, and DeJesus-Hernandez et al. (coriell.org)
  • However, protein levels of these variants were similar to controls, and analysis of patient frontal cortex and spinal cord tissue showed that the transcribed expanded GGGGCC repeat formed nuclear RNA foci, suggesting a gain-of-function mechanism. (coriell.org)
  • 2011) identified the GGGGCC expanded repeat as a cause of FTD/ALS in families reported by Pearson et al. (coriell.org)
  • TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by the TARDBP gene. (wikipedia.org)
  • The NOP56 gene mutations that cause SCA36 involve a string of six DNA building blocks (nucleotides) located in an area of the gene known as intron 1. (medlineplus.gov)
  • In healthy individuals, GGCCTG is repeated 3 to 14 times within the gene. (medlineplus.gov)
  • However, a large increase in the number of GGCCTG repeats in the NOP56 gene disrupts the normal structure of NOP56 mRNA. (medlineplus.gov)
  • Additionally, researchers believe that the large expansion of the hexanucleotide repeat in the NOP56 gene may reduce the activity of a nearby gene called MIR1292 . (medlineplus.gov)
  • Some of these tools are designed to detect STR expansions at disease-related loci, while others detect expansions and contractions of STRs genome-wide but are constrained by sequencing read length and the STR motif size. (biomedcentral.com)
  • The mutation, called a hexanucleotide repeat expansion, is an unusual one that involves repeating a DNA sequence over and over again. (nih.gov)
  • 30 repeats of this hexanucleotide, approximately 8-10% of FTD and ALS European patients carry very large expansions which have been reported to range between 700 and 1,600 repeats 5 . (nature.com)
  • 2011). Affected individuals had expanded repeat units ranging from 700 to 1,600. (coriell.org)
  • A variety of chemical modifications decorate the nucleic acids, increasing the alphabet of DNA to about a dozen known nucleotide variants. (pharmaceuticalintelligence.com)
  • NIA and NINDS also funded work by a team from the Mayo Clinic in Florida, reported by Mayo investigator Rosa Rademakers, Ph.D., and colleagues, which independently identified the same repeat DNA sequence as a genetic cause of FTD/ALS. (nih.gov)
  • scolymus) has been used to catalog the genome's content of simple sequence repeat (SSR) markers. (researchgate.net)
  • The negative supercoiling of DNA can induce sequence-dependent conformational changes that give rise to local DNA structures and alternative DNA conformations such as cruciforms, A-DNA, left-handed DNA (Z-DNA), triplexes, four-stranded DNA (quadruplexes) and others [ 2 , 3 ]( ref )" But we don't really get into most of those other types here. (anti-agingfirewalls.com)
  • G-rich sequences have a propensity for forming highly stable quadruplex structures in both RNA and DNA termed G-quadruplexes. (nature.com)
  • Perfect repeats mutate about 2 × more often than imperfect repeats. (biomedcentral.com)
  • Short tandem repeats (STRs), or microsatellites, are 1-6 base pair (bp) motifs of repeating units of DNA. (biomedcentral.com)
  • This string of six nucleotides (known as a hexanucleotide) is represented by the letters GGCCTG and normally appears multiple times in a row. (medlineplus.gov)
  • The secondary structure of the hexanucleotide repeat is very likely to be involved in determining the proteins it interacts with. (nature.com)
  • Repeat-associated non-AUG translation of this expansion produces dipeptide repeat proteins (DRPs). (frontiersin.org)
  • This enabled the diversified complementarity and secondary structures that allow RNA species to specifically interact with other components of the cellular machinery such as DNA and proteins. (pharmaceuticalintelligence.com)
  • Alternative splicing of MAPT pre-mRNA generates six major tau isoforms in the adult central nervous system resulting in tau proteins with three or four microtubule-binding repeat domains. (biomedcentral.com)
  • These unusual DNA structures play critical roles in regulation of very basic biological functions and are integral part of the complex regulatory systems of living beings. (anti-agingfirewalls.com)
  • G-quadruplexes are secondary semi-stable folded structures found in our DNA and RNA which tend to assemble around guanine-rich sequences in the presence of cation molecules like potassium. (anti-agingfirewalls.com)
  • Both RRMs follow this pattern: β1-α1-β2-β3-α2-β4-β5, which allows them to bind to both RNA and DNA onto U G/T G-repeats of 3'UTR (Untranslated Terminal Regions) end of mRNA/DNA. (wikipedia.org)
  • 2019. Effect of trinucleotide repeat expansion on the expression of TCF4 mRNA in Fuchs' endothelial corneal dystrophy . (cardiff.ac.uk)
  • The formation (folding) of DNA G-quadruplexes and the unfolding of G-quadruplex structures to allow telomerease to work is highly evolved. (anti-agingfirewalls.com)
  • These modifications influence many cellular processes including transcription, RNA processing, signal transduction cascades, DNA damage response, and liquid-liquid phase separation ( Guccione and Richard, 2019 ). (frontiersin.org)
  • And, G-quadruplex formation on single stranded DNA is one of the ways that the telomeric DNA is protected from oxidative stress and from triggering the DNA-damage response (DDR), which causes cellular senescence. (anti-agingfirewalls.com)
  • Longer repeats were associated with the A allele at SNP rs3849942, which marked a disease haplotype. (coriell.org)
  • Further analysis identified this expanded hexanucleotide repeat in 16 (61.5%) of a series of 26 families with the disorder, as well as in 11.7% of familial FTD and 23.5% of familial ALS from 3 patient series. (coriell.org)
  • These can occur in both DNA and RNA and consist of stacks of planar layers of G-tetrad units, named G-quartets in which the G bases are arranged in a square cyclic pattern held together by eight hydrogen bonds ( Fig. 1a ). (nature.com)
  • In addition, an expanded repeat was found in 102 (38.1%) of 268 familial ALS probands of European origin. (coriell.org)
  • FISH studies showed that the expansion in a family from Wales (Pearson et al. (coriell.org)
  • 2011). The expanded repeat was also found in 46.4% of Finnish familial ALS cases and in 21% of sporadic cases. (coriell.org)
  • TAR DNA-binding protein 43 (TDP-43) is a ubiquitously expressed RNA-binding protein with diverse roles in RNA processing. (lafurnitura.com)
  • At NIH, our state of the art DNA sequencing facilities enabled us to rapidly generate the data needed to identify this repeat expansion. (nih.gov)