• 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)
  • 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)
  • 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)
  • 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)
  • intron
  • 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)
  • phenotypes
  • 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)
  • 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)
  • causative gene
  • In August 1999, 16 years after meeting her first patient with Rett syndrome, Zoghbi and collaborators identified MECP2 as the causative gene. (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)
  • diseases
  • An inverse correlation between the repeat length and disease severity/earlier age of onset, known as anticipation, has been observed in most of the families transmitting such types of diseases, suggesting that the length change of the repeats may play a role in the manifestation of anticipation. (springer.com)
  • As more repeat expansion diseases have been discovered, several categories have been established to group them based upon similar characteristics. (wikipedia.org)
  • Although these diseases share the same repeated codon (CAG) and some symptoms, the repeats for the different polyglutamine diseases occur on different chromosomes. (wikipedia.org)
  • pathogenic
  • A limitation to this test is that if the number of CAG repeats in an individual being tested falls between the healthy and pathogenic ranges (45-60 repeats), then the test cannot predict whether an individual will have MJD symptoms. (wikipedia.org)
  • disease
  • Thirty-four percent of FECD subjects and 5% of control individuals harbor more than 50 trinucleotide repeats, which was considered as the disease threshold. (arvojournals.org)
  • Only three motifs, CAG/CTG, CGG/CCG, and GAA/TTC, of the 10 possible trinucleotide repeat permutations have so far been associated with human disease. (springer.com)
  • The size of the repeat correlates with severity of the disease. (wikipedia.org)
  • The lab's current projects include: locating human sleep genes, uncovering the molecular mechanisms of human sleep regulation and human circadian rhythms, investigating mouse models with de/dys-myelinating disease, and classifying miRNAs that contribute to healthy myelin. (wikipedia.org)
  • They determined that the disease was caused by an expansion of the glutamine-coding CAG trinucleotide repeat in this gene. (wikipedia.org)
  • MJD is an autosomal dominant disease, meaning that if either parent gives the defective gene to a child, the child will show symptoms of the disease. (wikipedia.org)
  • 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)