PubMed · 7874160
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P J Willems. 1994. Dynamic mutations hit double figures.. https://doi.org/10.1038/ng1194-213
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BACKGROUND: Fragile X syndrome is gonosomal recessive mental retardation with the frequency 1:1000 in male population. Fragile X syndrome is caused by amplification of CGG repeat in 1. exon of FMT-1 gene. The aim of this study was to set up and validate a rapid and efficient PCR diagnosis to select FRAXA negative patients in population of mental retarded patients. METHODS AND RESULTS: In the set up phase of the method, 196 patients were diagnosed. We were using modified radioactive PCR of CGG. Obtained PCR fragments were separated on 6% denaturing PAGE. Results were correlated with Southern blot analysis using pE5.1 probe. STR-PCR was verified on a large set of patients and shows validity and efficiency of results in the case of pre- and full mutations in male hemizygous patients too. For estimation of carriers with pre- and full mutation by females modified diagnostic approach was developed. There was no difference found between results from PCR and Southern blot analysis. CONCLUSIONS: The PCR method is convenient not only for selection of FRAXA negative patients, but for diagnosis of full mutation and premutation of affected probands.
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Infection of human cells with adenovirus 12 (Ad12), but not Ad2 or 5, induces four specific sites of metaphase chromosome fragility: the U1 small nuclear RNA (snRNA) genes (the RNU1 locus), the U2 snRNA genes (RNU2), the U1 snRNA pseudogenes (PSU1) and the 5S rRNA genes (RN5S). Significantly, each of these sites corresponds to a multigene family encoding a small, abundant structural RNA. We and others have shown previously that Ad12-induced fragility of the RNU2 locus requires U2 snRNA promoter elements, viral early functions and p53 function, but not viral replication or integration, Rb function or chromosomal sequences flanking the RNU2 locus. Remarkably, we now find that very low doses of actinomycin D (5-50 ng/ml) can phenocopy Ad12 infection: metaphase fragility of the RNU1 and RNU2 loci is induced specifically in the absence of virus, and induction also requires U2 promoter elements and p53 function. Concurrently, it has been found by others that treatment with cytosine arabinoside (araC), but not aphidicolin, can also phenocopy Ad12 infection. We propose that Ad12 infection, actinomycin D and araC all induce a similar or identical global damage arrest signal (perhaps a modification or altered conformation of p53) that preferentially interferes with metaphase condensation of the RNU1 and RNU2 loci. The RNU1 and RNU2 loci could be especially sensitive to this global signal either because specialized U snRNA transcription factors interact uniquely with the signal, or because the high concentration of short, active transcription units hinders chromatin condensation.