Identification Of The Sca10 Mutation

Because SCA10 is an ADCA with anticipation1-3 and several other SCA subtypes are associated with trinucleotide repeat expansions, the mutation responsible for SCA10 might also be an expansion of an unstable triplet repeat. Matsuura et al2 and Zu et al3 independently mapped the SCA10 locus to the chromosome 22q13-qter region by linkage analyses. Two recombination events in these two families indicated that the SCA10 gene resides within a 3.8-cM interval between D22S1140 and D22S1160. Studies...

DNA Repair

Methyl-directed mismatch repair (MMR) In all organisms genomic integrity is normally maintained by a variety of DNA repair pathways, including MMR and nucleotide excision repair (NER).61 Secondary DNA structures formed during DNA synthesis, especially within single-stranded regions containing repetitive tracts, may be hazardous for genome stability if not removed by repair activities. MMR pathway is a fundamental system involved in maintaining genomic integrity because in addition to correcting...

Mouse Models Of Unstable

In order to provide a system in which the factors effecting repeat stability may be more precisely defined, a number of mouse models containing expanded CTG CAG repeat arrays have been generated. These include models for a number of loci and with varying amounts of flanking DNA in simple transgenics,11-19 and more recently recombination into the murine homologue.20-22 To date, two models using transgenes derived from the human DM1 locus have been reported14,16 (Fig. 1A). The Dmt162 transgene...

Deficiency Of Six5 In Dm1

There are several genes in the region surrounding the CTG repeat at the DM1 locus45 (Fig. 1B), which led to the hypothesis that the expanded repeat might alter the expression of genes in addition to DMPK. Repetitive elements in other areas of the genome, for example at the heterochromatin of telomeres and centromeres, were known to suppress the expression of adjacent genes. For example, studies in Drosophila and other organisms demonstrated that genes positioned adjacent to regions of...

Frataxin Structure And Function

Frataxin does not resemble any protein of known function. It aminoacid sequence does not predict any transmembrane domain. It is highly conserved during evolution,4 with homologs in mammals, invertebrates, yeast and plants. The protein is targeted to the mitochondria,70,78,79 as first discovered by observing the intracellular localization of frataxin-green fluorescent protein GFP fusion proteins.78,80 The mitochondrial localization of endogenous frataxin was then demonstrated by...