• locus
  • Since 2001 it has been discovered that DM2 is caused by a CCTG (cytosine-cytosine-thymine-guanine) expansion on chromosome 3 at locus 3q21, but as of 2004 it is not known how this repeat affects muscle cell function. (thefreedictionary.com)
  • Dominance in genetics is a relationship between alleles of one gene, in which the effect on phenotype of one allele masks the contribution of a second allele at the same locus. (wikipedia.org)
  • alleles
  • The alleles, which are a variant form of a gene involved in this form of MD are: PABPN1, (GCG)n EXPANSION, (GCG)8-13, PABPN1, (GCG)n EXPANSION, (GCG)7 and PABPN1, GLY12ALA. (wikipedia.org)
  • Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. (wikipedia.org)
  • More generally, where a gene exists in two allelic versions (designated A and a), three combinations of alleles are possible: AA, Aa, and aa. (wikipedia.org)
  • Thus, each gene also has a corresponding homologue, which may exist in different versions called alleles. (wikipedia.org)
  • 1997
  • A plasmid encoding the binding activity was purified and used to clone the complete bruno gene (Webser, 1997). (sdbonline.org)
  • sequence
  • 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)
  • An expression screen based on the binding of Bru to its target sequence was designed in order to identify the gene coding for Bruno. (sdbonline.org)
  • There is a CAG repeat in the coding sequence which is longer in humans than other species (6-38 uninterrupted CAG repeats in healthy humans versus 2 in the mouse gene). (wikipedia.org)
  • symptoms
  • In general, the more repeats in the affected range that someone has, the earlier the age of onset of symptoms and the more severe the symptoms. (thefreedictionary.com)
  • It is not possible to look at a person's repeat number and predict at what age they will begin to have symptoms or how their condition will progress. (thefreedictionary.com)
  • 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)
  • 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)
  • How the polyglutamine expansion in ataxin-2 leads to these symptoms is unknown. (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)
  • citation needed
  • citation needed] There have been reported cases where a polyglutamine expansion may lengthen when passed down, which often can result in an earlier age-of-onset and a more severe disease phenotype for individuals who inherit the disease allele. (wikipedia.org)
  • citation needed] Recent results suggest that the CAG repeats need not always be translated in order to cause toxicity. (wikipedia.org)
  • humans
  • a region of DNA with a high concentration of CpG sequences that often associate with gene promoters in humans. (udel.edu)
  • This elongation is variable in length, with as few as 6 and as many as 81 repeats reported in humans. (wikipedia.org)
  • Most vertebrates have two orthologs of the gene (called ATXN2 and ATXN2L in humans), with the exception of birds which only have one. (wikipedia.org)
  • Humans with this autosomal dominant disease typically go to bed around 7:00 p.m. and wake up at 3:00 a.m. (wikipedia.org)
  • Blood types in humans is determined by a gene that creates an A, B, AB or O blood type and is located in the long arm of chromosome nine. (wikipedia.org)
  • Disease
  • An expansion of the trinucleotide (GCN) repeat from normal 10 to 11-17 at the 5' end of the coding region of this gene leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. (wikipedia.org)
  • Machado-Joseph disease is a type of spinocerebellar ataxia and is the most common cause of autosomal-dominant ataxia. (wikipedia.org)
  • 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)
  • This, in turn, could alter the expression of the genes ataxin-1 regulates, leading to disease. (wikipedia.org)
  • The disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100, and can expand in size when transmitted to successive generations. (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)
  • 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)
  • Longer repeats are usually associated with earlier onset and more severe disease. (wikipedia.org)
  • The second, related 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 CGG repeat. (wikipedia.org)
  • Identifying trinucleotide repeats as the basis of disease has brought clarity to our understanding of a complex set of inherited neurological diseases. (wikipedia.org)
  • Although the causative genes are widely expressed in all of the known polyglutamine diseases, each disease displays an extremely selective pattern of neurodegeneration. (wikipedia.org)
  • In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. (wikipedia.org)
  • cDNA
  • Our approach is to combine physiological approaches (how fast, how steeply voltage-dependent, how is signal transduced) and biochemical experiments using cDNA microarrays (which genes, in what context, what relationship to learning and memory). (stanford.edu)
  • mutant
  • Children of an affected parent have a 50% chance of inheriting the mutant gene. (wikipedia.org)
  • In cell-based assays, it was found that these mutant channels aggregate in the endoplasmic reticulum, not dissimilar from that seen in the CAG expansion mutants above. (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)
  • neuronal
  • We study how synaptic transmission and depolarization cause changes in neuronal gene expression. (stanford.edu)
  • One example of such signaling involves a local increase in Ca2+ concentration near a class of Ca2+ channels (L-type) different from those that trigger presynaptic transmitter release, subsequently leading to activation of an exemplar transcription factor, CREB, a regulator of transcription of many important neuronal genes. (stanford.edu)
  • How polyglutamine expansion in Ataxin-1 causes neuronal dysfunction and degeneration is still unclear. (wikipedia.org)
  • targeting human
  • Huntingtin lowering is achieved using gene transfer of a cassette encoding an engineered microRNA targeting human HTT, delivered via adeno-associated viral vector serotype 5 (AAV5-miHTT). (nusl.cz)