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  • proteins
  • Unexpectedly, we discovered that CAG expansion constructs express homopolymeric polyglutamine, polyalanine, and polyserine proteins in the absence of an ATG start codon. (jove.com)
  • Additionally, we show that RAN translation across human spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1) CAG expansion transcripts results in the accumulation of SCA8 polyalanine and DM1 polyglutamine expansion proteins in previously established SCA8 and DM1 mouse models and human tissue. (jove.com)
  • Introns are found in the genes of most organisms and many viruses, and can be located in a wide range of genes, including those that generate proteins , ribosomal RNA (rRNA), and transfer RNA (tRNA). (wn.com)
  • When proteins are generated from intron-containing genes, RNA splicing takes place as part of the RNA processing pathway that follows transcription and precedes translation . (wn.com)
  • DM arises from the expansion of two similar non-coding microsatellites in the DMPK and CNBP genes which have been proposed to cause disease through a common mechanism, a toxic RNA gain-of-function which can either inhibit or activate specific proteins. (ufl.edu)
  • One of these candidates, the muscleblind-like (MBNL) family of proteins encoded by three genes, MBNL1, MBNL2, and MBNL3, are sequestered into discrete nuclear foci by RNA repeat expansions, preventing interactions with endogenous RNA targets and compromising their activity. (ufl.edu)
  • genetic
  • Although the transfer of a number of genes from these organelles to the nucleus prevents them from living independently, each still possesses genetic material in the form of double stranded DNA. (wikipedia.org)
  • However, when used to refer to the number of repeating units of genetic information that are sufficient to encode the blueprint for something as complex as a human being, it never ceases to amaze me that this number is big enough! (bmj.com)
  • The increasing availability of DNA amplification by PCR at the beginning of the 1990s triggered a large number of studies using the amplification of microsatellites as genetic markers for forensic medicine, for paternity testing, and for positional cloning to find the gene underlying a trait or disease. (wikipedia.org)
  • specific genes
  • Category I includes Huntington's disease (HD) and the spinocerebellar ataxias that are caused by a CAG repeat expansion in protein-coding portions of specific genes. (wikipedia.org)
  • This and additional evidence supports the hypothesis that loss of MBNL1 function in DM causes defects in the alternative splicing of specific genes during postnatal development which leads to distinct pathological features in adult-onset disease, including myotonia and insulin insensitivity. (ufl.edu)
  • DMPK
  • Myotonic dystrophy type 1 (DM1) is a neuromuscular disease caused by the expansion of a CTG repeat in the DMPK gene and characterised by progressive skeletal muscle weakness and wasting. (jove.com)
  • codons
  • Due to the triplet nature of gene expression by codons, the insertion or deletion can change the reading frame (the grouping of the codons), resulting in a completely different translation from the original. (wikipedia.org)
  • Huntington's
  • Although the presence of these subtle mechanisms may be beneficial to a whole population, when they go wrong, as is thought to happen in the case of human trinucleotide repeat associated diseases, such as Huntington's disease, the consequences for the individual can be fatal. (bmj.com)
  • The (CTG.CAG)N repeats in the Huntington's disorder (HD) is ELTD1 one of the most highly variable TRS in the human population . (cancer-basics.com)
  • Protein
  • Human genomes include both protein-coding DNA genes and noncoding DNA . (wikipedia.org)
  • Most (though probably not all) genes have been identified by a combination of high throughput experimental and bioinformatics approaches, yet much work still needs to be done to further elucidate the biological functions of their protein and RNA products. (wikipedia.org)
  • There are an estimated 19,000-20,000 human protein-coding genes. (wikipedia.org)
  • These diseases are characterized by typically much larger repeat expansions than the first two groups, and the repeats are located outside of the protein-coding regions of the genes. (wikipedia.org)
  • Trinucleotide expansions cause disease by both protein- and RNA-mediated mechanisms. (jove.com)
  • The human androgen receptor (AR) is a protein encoded by a gene located on the proximal long arm of the X chromosome (locus Xq11-Xq12). (wikipedia.org)
  • androgen
  • 4, 10 Hypospadias is also a manifestation in some rare single gene traits affecting sex differentiation, for example, the X linked partial androgen insensitivity syndrome and the recessive 5-alpha-reductase deficiency. (bmj.com)
  • This combination functions as a transcription complex to turn on androgen gene expression. (wikipedia.org)
  • loci
  • To investigate the incidence of the SCA in Southern Brazil, we analyzed the trinucleotide repeats (CAG)n at the SCA1, SCA2, SCA3, SCA6 and SCA7 loci to identify allele size ranges and frequencies. (readbyqxmd.com)
  • disorder
  • Expanded SCA1 and CAG repeats were found to cosegregate with the disorder in six of the families tested and were also observed in one sporadic individual with a negative family history of SCA. (springer.com)
  • The invention for the first time provides strong evidence of a susceptibility gene for bipolar mood disorder that is located in the 18q22-q23 region of the long arm of chromosome 18. (google.com)
  • phenotype
  • Thus, the phenotype of traits linked to genes found in either chloroplasts or mitochondria are determined exclusively by the maternal parent. (wikipedia.org)
  • transcription
  • We record that repeats possess the to hinder the binding of transcription elements with their consensus series by changed DNA inhaling and exhaling dynamics in closeness from the binding sites. (cancer-basics.com)
  • consist
  • The telomeres at the ends of the chromosomes, thought to be involved in ageing/senescence, consist of repetitive DNA, with the hexanucleotide repeat motif TTAGGG in vertebrates. (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)
  • pathogenic
  • Additionally, we show that MBNL1 interacts with DM1 pathogenic and non-pathogenic repeat RNAs, but inherent differences in these interactions contribute to the ability to promote disease associated changes in alternative splicing. (ufl.edu)
  • SCA1
  • Three genes, SCA1 on 6p, SCA2 on 12q and MJD1 on 14q, have been isolated for SCA1, SCA2 and Machado-Joseph disease (MJD), respectively. (springer.com)
  • A total of 14 South African kindreds and 22 sporadic individuals with SCA were investigated for the expanded SCA1 and MJD repeats. (springer.com)
  • The use of the microsatellite markers D6S260, D6S89 and D6S274 provided evidence that the expanded SCA1 repeats segregated with three distinct haplotypes in the six families. (springer.com)
  • humans
  • Nevertheless, even focusing as intended upon microsatellites and their relevance to humans, it should become clear that most of these questions remain ones that will require consideration, even if only in passing. (bmj.com)
  • foci
  • 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)
  • intron
  • The word intron is derived from the term intragenic region , i.e. a region inside a gene. (wn.com)
  • overexpression
  • 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)
  • strand
  • Four divergent domains consisted of microsatellite repeats biased in composition with purines on one strand and pyrimidines on the other, including mononucleotide repeats of C:G base pairs approximately 20 bp in length. (wikipedia.org)
  • found
  • We have found that the gain of novel LCRs is frequently associated with repeat expansion whereas the loss of LCRs is more often due to accumulation of amino acid substitutions as opposed to deletions. (biomedsearch.com)
  • Thus
  • The Mre11 complex thus appears to be directly involved in removing CAG or CTG hairpins that arise frequently during DNA synthesis accompanying gene conversion of these trinucleotide repeats. (embopress.org)
  • distinct
  • Our working hypothesis is that MBNL genes show distinct temporal and spatial expression patterns that influence age-of-onset and disease-associated pathological changes. (ufl.edu)
  • 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)
  • short
  • For example, minisatellite DNA is a short region (1-5kb) of 20-50 repeats. (wikipedia.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)
  • There are several families of interspersed repetitive DNA, although the two largest are known as short and long interspersed nuclear elements (SINEs and LINEs, respectively), 1 and it is to the SINE family that the frequently mentioned Alu repeat belongs. (bmj.com)
  • human
  • The human homolog of mbl, MBNL1, which was originally identified as binding CUG repeats in RNA, has since been shown to bind CAG (and CCG) repeats as well. (wikipedia.org)
  • To investigate the effects of the CTG expansion on the physiological function of the skeletal muscles, we have used a transgenic mouse model carrying the human DM1 region with 550 expanded CTG repeats. (jove.com)