کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2146188 1548318 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evidence for chromosome fragility at the frataxin locus in Friedreich ataxia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Evidence for chromosome fragility at the frataxin locus in Friedreich ataxia
چکیده انگلیسی


• The region of chromosome 9 that contains the Frataxin (FXN) locus is prone to breakage and rearrangements.
• Friedreich ataxia (FRDA) is caused by a GAA/TTC-repeat expansion in the FXN gene
• FRDA alleles are prone to chromosome rearrangements induced by an ATM inhibitor.

Friedreich ataxia (FRDA) is a member of the Repeat Expansion Diseases, a group of genetic conditions resulting from an increase/expansion in the size of a specific tandem array. FRDA results from expansion of a GAA/TTC-tract in the first intron of the frataxin gene (FXN). The disease-associated tandem repeats all form secondary structures that are thought to contribute to the propensity of the repeat to expand. The subset of these diseases that result from a CGG/CCG-repeat expansion, such as Fragile X syndrome, also express a folate-sensitive fragile site coincident with the repeat on the affected chromosome. This chromosome fragility involves the generation of chromosome/chromatid gaps or breaks, or the high frequency loss of one or both copies of the affected gene when cells are grown under folate stress or as we showed previously, in the presence of an inhibitor of the ATM checkpoint kinase. Whether Repeat Expansion Disease loci containing different repeats form similar fragile sites was not known. We show here that the region of chromosome 9 that contains the FXN locus is intrinsically prone to breakage in vivo even in control cells. However, like FXS alleles, FRDA alleles show significantly elevated levels of chromosome abnormalities in the presence of an ATM inhibitor, consistent with the formation of a fragile site.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 781, November 2015, Pages 14–21
نویسندگان
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