• 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)
  • During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. (bvsalud.org)
  • 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)
  • Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. (bvsalud.org)
  • Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by the genomic expansion of CTG repeats, in which RNA-binding proteins, such as muscleblind-like protein, are sequestered in the nucleus, and abnormal splicing is observed in various genes. (bvsalud.org)
  • 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)
  • 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)
  • Translation of these repeat expansions occurs mostly through two mechanisms. (wikipedia.org)
  • 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)
  • 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)
  • Sometimes, a person may have more than the usual number of copies of a repeat sequence associated with a gene, but not enough to alter the function of that gene. (wikipedia.org)
  • These findings suggest a functional interplay between the two RPAs where Alt-RPA may antagonistically offset RPA's suppression of disease-associated repeat expansions, which may extend to other DNA processes. (bvsalud.org)
  • Negative association findings and research involving the serotonin transporter gene, FMR1, RELN, WNT2, HOXA1, and HOXB1 genes may be found elsewhere on this site . (neurotransmitter.net)
  • 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 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)
  • In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region. (neurotransmitter.net)
  • 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)
  • Other expanded repeats can be translated into proteins containing a pathogenic stretch of repeated amino acids by a novel mechanism called repeat-associated non-AUG (RAN) translation [ 12 ], and these proteins could contain compositionally biased amino acids. (biomedcentral.com)
  • Trinucleotide repeats are a subset of a larger class of unstable microsatellite repeats that occur throughout all genomes. (wikipedia.org)
  • The (CTG · CAG) n repeat expansion is highly unstable and almost always changes in size on transmission: the repeat expansion is more likely to become larger when maternally transmitted and more likely to contract with paternal transmission. (nih.gov)
  • Huntington disease (HD) is an inherited neurodegenerative disease caused by an abnormal expansion of a CAG repeat in the huntingtin HTT ( HD ) gene. (biomedcentral.com)
  • Huntington disease (HD) is an autosomal dominantly transmitted, progressive neurodegenerative disease associated with a polymorphic CAG trinucleotide repeat in the 5' part of the HTT ( HD ) gene, which is expanded and translated into an elongated polyglutamine tract in the huntingtin protein [ 1 ]. (biomedcentral.com)
  • In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. (wikipedia.org)
  • 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)
  • The diagnosis of SCA8 is established in a proband with suggestive findings and a heterozygous abnormal (CTG · CAG) n repeat expansion in the two overlapping genes ATXN8OS/ATXN8 identified by molecular genetic testing . (nih.gov)
  • To date, all individuals diagnosed with SCA8 whose parents have been evaluated with molecular genetic testing have one parent with an ATXN8OS/ATXN8 (CTG · CAG) n repeat expansion. (nih.gov)
  • Once an SCA8 (CTG · CAG) n repeat expansion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. (nih.gov)
  • 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)
  • Therefore, we applied this method to analyze the NIIs of diseased human brains, which may have proteins with compositionally biased regions, and identified a serine-rich protein called hornerin. (biomedcentral.com)
  • Translation of these repeat expansions occurs mostly through two mechanisms. (wikipedia.org)
  • In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes. (wikipedia.org)
  • The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. (wikipedia.org)
  • Androgen hyposensitivity, caused by long AR CAG repeats, may increase the risk of breast cancer in men. (nih.gov)
  • Sibs who inherit a (CTG · CAG) n repeat expansion may or may not develop clinical manifestations of SCA8. (nih.gov)
  • Trinucleotide repeat disorders and the related microsatellite repeat disorders affect about 1 in 3,000 people worldwide. (wikipedia.org)
  • 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)
  • There was no correlation between AR CAG repeat length and age at diagnosis. (nih.gov)
  • Some carriers, during the formation of eggs or sperm, may give rise to higher levels of repetition of the repeat they carry. (wikipedia.org)
  • Yet, despite this strong correlation, there remains considerable variation in AO (of more than 40 years) in individuals with identical repeat lengths. (biomedcentral.com)
  • A CAG repeat polymorphism in the androgen receptor gene is associated with reduced bone mass and increased risk of osteoporotic fractures. (nih.gov)
  • 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)