Nov 21, 2016

Age-related length variability of polymorphic CAG repeats

DNA Repair
Monica Sanchez-Contreras, Fernando Cardozo-Pelaez

Abstract

Somatic instability of CAG repeats has been associated with the clinical progression of CAG repeat diseases. Aging and DNA repair processes influence the somatic stability of CAG repeat in disease and in mouse models. However, most of the studies have focused on genetically engineered transgenic repeats and little is known about the stability of naturally polymorphic CAG repeats. To study whether age and/or DNA repair activity have an effect on the somatic stability of CAG repeats, we analyzed variations of the length of naturally polymorphic CAG repeats in the striatum of young and aged WT and ogg1 KO mice. Some multiple and long polymorphic CAG repeats were observed to have variable length in the striatum of aged mice. Interestingly, a low level of repeat variability was detected in the CAG repeat located in tbp, the only mouse polymorphic CAG repeat that is associated with a trinucleotide disease in humans, in the striatum of aged mice and not in young mice. We propose that age may have an effect on the somatic stability of polymorphic CAG repeats and that such an effect depends on intrinsic CAG repeat characteristics.

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Mentioned in this Paper

Maintenance of DNA Trinucleotide Repeats
Gene Polymorphism
Study
Chorionic alpha(2)-microglobulin
OGG1 gene
Neostriatum
DNA Repair
Base Excision Repair
Lentiform Nucleus Structure
Senility

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