• proteins
  • Our long-term goal is to identify the critical genes and cellular pathways affected by misfolded human disease proteins. (stanford.edu)
  • Nucleotide excision repair proteins are mobilized to this area where one likely outcome is the expansion of nucleotides in the template strand while the other is the absence of nucleotides. (wikipedia.org)
  • If these repeats are found in coding regions then the variations to the polynucleotide sequence can result in the formation of abnormal proteins in eukaryotes. (wikipedia.org)
  • citation needed] Currently, nine neurologic disorders are known to be caused by an increased number of CAG repeats, typically in coding regions of otherwise unrelated proteins. (wikipedia.org)
  • intron
  • Purification of genomic DNA from each patient's blood sample was carried out and the expansion of CTG repeats in the third intron of TCF4 was subsequently examined by polymerase chain reaction (PCR). (arvojournals.org)
  • If the repeat is present in an intron it can cause toxic effects by forming spherical clusters called RNA foci in cell nuclei. (wikipedia.org)
  • polymorphism
  • We investigated the association between polymorphism in the androgen receptor ( AR ) and vitamin D receptor ( VDR ) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. (aacrjournals.org)
  • Investigations of the relation between the AR polymorphism and breast cancer ( Table 1 ) have been conflicting, variably reporting that short repeats are associated with a decreased risk ( 14 - 18 ) or are not associated with risk ( 19 - 21 ) or are associated with decreased breast cancer survival ( 16 , 22 , 23 ). (aacrjournals.org)
  • mediate
  • The mechanism by which trinucleotide secondary structures mediate expansions is not well understood. (embopress.org)
  • Thus the AR activates these genes to mediate the effects of androgens in the human body, including the development and maintenance of the male sexual phenotype and generalized anabolic effects. (wikipedia.org)
  • 1993
  • On the same day in April 1993, both Zoghbi and Orr identified ATXN1 as the gene responsible for SCA1. (wikipedia.org)
  • atrophy
  • These disorders are characterized by autosomal-dominant mode of inheritance (with the exception of spino-bulbar muscular atrophy, which shows X-linked inheritance), midlife onset, a progressive course, and a correlation of the number of CAG repeats with the severity of disease and the age at onset. (wikipedia.org)
  • polyQ
  • Furthermore, when the CAG repeat was changed to a repeating series of CAACAG (which also translates to polyQ), toxicity was dramatically reduced. (wikipedia.org)
  • locus
  • Overexpression of Mre11p or Rad50p suppresses the inhibition of DSB repair by CAG 98 and significantly increases the average size of expansions found at the recipient locus. (embopress.org)
  • An individual who is not affected by Huntington's disease will have 6-35 tandem repeats at the HD locus. (wikipedia.org)
  • several genes
  • It appears to be involved in regulating gene expression based on its location in the nucleus of the cell, its association with promoter regions of several genes, and its interactions with transcriptional regulators and parts of the RNA splicing machinery. (wikipedia.org)
  • microsatellites
  • This class of microsatellites has the property of undergoing rapid and sometimes massive expansion of their repeat number, during germline transmission or early embryogenesis. (embopress.org)
  • One striking feature of all expansion‐associated microsatellites is their propensity to form secondary structures. (embopress.org)
  • sequence
  • Expansions are apparently dependent on the property of the repeat array to form hairpins, since DSB repair of a CAA 87 repeat induces only contractions of the repeat sequence. (embopress.org)
  • In people who have DM1, this sequence of nucleotides is repeated too many times-more than the normal number of 37 times-and thus this section of the gene is too big. (thefreedictionary.com)
  • A slippage event normally occurs when a sequence of repetitive nucleotides (tandem repeats) are found at the site of replication. (wikipedia.org)
  • The sequence of the ATN1 gene contains a nuclear localizing signal (NLS) and a nuclear export signal (NES). (wikipedia.org)
  • heterozygous
  • The gene expression, called heterozygous-normal/low may cause PCOS-like excessive follicle-activity and hyperactive ovarian function when women are younger. (wikipedia.org)
  • fragile
  • 4-40 CGG repeats in this gene is considered normal, while individual with >200 repeats have full Fragile X Syndrome. (wikipedia.org)
  • While there, she was part of the team that identified the fragile-X syndrome gene. (wikipedia.org)
  • Minor expansions of CGG repeats that do not cause fragile X syndrome are associated with an increased risk for premature ovarian aging, also called occult primary ovarian insufficiency, a condition in which women prematurely deplete their ovarian function. (wikipedia.org)
  • disorders
  • As in several other trinucleotide-repeat disorders, there is a strong association between repeat length and age at disease onset, with higher repeat length leading to earlier onset. (bmj.com)
  • Current work in Zoghbi's lab strives to determine specific neuronal populations that contribute to phenotypes observed in MECP2 disorders through deletion of the gene in select cell types. (wikipedia.org)
  • unclear
  • The heritability of autism, however, is complex, and it is typically unclear which genes are responsible. (wikipedia.org)
  • tracts
  • Repeats of 39 or more uninterrupted CAG triplets cause disease, and longer repeat tracts are correlated with earlier age of onset and faster progression. (wikipedia.org)
  • replication
  • Recombination induced by double‐strand breaks (DSBs) in yeast leads to a higher proportion of expansions to contractions than does replication‐associated tract length changes. (embopress.org)
  • Slippage occurs through five main stages: In the first step, DNA polymerase encounters the direct repeat during the replication process. (wikipedia.org)
  • DNA polymerase reassembles its position on the template strand and resumes normal replication, but during the course of reassembling, the polymerase complex backtracks and repeats the insertion of deoxyribonucleotides that were previously added. (wikipedia.org)
  • Tandem repeats (the main influence for slippage replication) can be found in coding and non-coding regions. (wikipedia.org)
  • This repeat is prone to errors in DNA replication and can vary widely in length between individuals. (wikipedia.org)
  • significantly associated
  • In 2010, work from Aaron Gitler and Nancy Bonini at the University of Pennsylvania discovered that intermediate-size CAG repeat expansions are significantly associated with risk for developing amyotrophic lateral sclerosis (Lou Gehrig's disease). (wikipedia.org)
  • secondary
  • These data indicate that repair‐ associated DNA synthesis is inhibited by secondary structures formed by CAG 98 and that these structures promote repeat expansions during DSB repair. (embopress.org)