In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. (wikipedia.org)
These expanded repeats are transcribed and produce toxic CUG RNAs that sequester and inhibit activities of the MBNL family of developmental RNA processing factors. (bvsalud.org)
To address the molecular and cellular events that lead to these pathological outcomes, we recently generated a mouse Dmpk CTG expansion knock-in model and identified choroid plexus epithelial cells as particularly affected by the expression of toxic CUG expansion RNAs. (bvsalud.org)
Region3
The first main category these authors discuss is repeat expansions located within the promoter region of a gene or located close to, but upstream of, a promoter region of a gene. (wikipedia.org)
There is often increased methylation at CpG islands near the repeat region, resulting in a closed chromatin state, causing gene downregulation. (wikipedia.org)
Myotonic dystrophy type 1 is a dominantly inherited multisystemic disease caused by CTG tandem repeat expansions in the DMPK 3' untranslated region. (bvsalud.org)
Disease6
In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes. (wikipedia.org)
The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. (wikipedia.org)
Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. (wikipedia.org)
The second DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. (wikipedia.org)
The discovery that trinucleotide repeats could expand during intergenerational transmission and could cause disease was the first evidence that not all disease-causing mutations are stably transmitted from parent to offspring. (wikipedia.org)
The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. (wikipedia.org)
Toxic2
The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. (wikipedia.org)
This results in, variously, a toxic gain of function, a loss of function, a dominant negative effect and/or a mix of these mechanisms for the protein hosting the expansion. (wikipedia.org)
Autosomal dominant1
Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited disorder caused by expansion of a germline and somatically unstable CTG repeat in the DMPK gene. (nih.gov)
Nucleotide1
Many regions of the genome (exons, introns, intergenic regions) normally contain trinucleotide sequences, or repeated sequences of one particular nucleotide, or sequences of 2, 4, 5 or 6 nucleotides. (wikipedia.org)
Disorder2
However, the frequency of occurrence of any one particular repeat sequence disorder varies greatly by ethnic group and geographic location. (wikipedia.org)
In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. (wikipedia.org)
Disorders5
Trinucleotide repeat disorders, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides (trinucleotide repeats) increase in copy numbers until they cross a threshold above which they cause developmental, neurological or neuromuscular disorders. (wikipedia.org)
Trinucleotide repeat disorders and the related microsatellite repeat disorders affect about 1 in 3,000 people worldwide. (wikipedia.org)
Three categories of trinucleotide repeat disorders and related microsatellite (4, 5, or 6 repeats) disorders are described by Boivin and Charlet-Berguerand. (wikipedia.org)
The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. (wikipedia.org)
The third main category of trinucleotide repeat disorders and related microsatellite disorders is due to the translation of repeat sequenced into pathogenic proteins containing a stretch of repeated amino acids. (wikipedia.org)
Chromosome2
The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. (wikipedia.org)
The second DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. (wikipedia.org)
Size1
The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. (wikipedia.org)