Age-related length variability of polymorphic CAG repeats
Monica Sanchez-Contreras1, Fernando Cardozo-Pelaez2
1Department of Neuroscience, Birdsall Building, Mayo Clinic, 4500 San Pablo Road, 32224 Jacksonville, FL, USA; Department of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Skaggs Building 280, University of Montana, 59812 Missoula, MT, USA.
DNA Repair
|November 21, 2016
Summary
Aging influences the stability of naturally occurring CAG repeats in the brain. This CAG repeat instability may contribute to trinucleotide repeat diseases, with effects varying based on repeat characteristics.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Somatic instability of CAG repeats is linked to CAG repeat disease progression.
- Aging and DNA repair impact CAG repeat stability, but research often uses engineered repeats.
- The stability of naturally polymorphic CAG repeats remains understudied.
Purpose of the Study:
- To investigate the effects of age and DNA repair activity on the somatic stability of naturally polymorphic CAG repeats.
- To analyze CAG repeat length variations in the striatum of young and aged wild-type (WT) and ogg1 knockout (KO) mice.
Main Methods:
- Analysis of naturally polymorphic CAG repeat length variations.
- Comparison between young and aged WT and ogg1 KO mice.
- Focus on CAG repeats in the striatum.
Main Results:
- Variable CAG repeat lengths were observed in the striatum of aged mice.
- Aged mice showed low-level variability in the TBP CAG repeat, a naturally polymorphic repeat linked to human trinucleotide diseases.
- No significant variability was detected in young mice.
Conclusions:
- Age may affect the somatic stability of polymorphic CAG repeats.
- The impact of aging on CAG repeat stability appears dependent on intrinsic repeat characteristics.
- Findings suggest a potential role for age-related instability in naturally occurring CAG repeats relevant to human diseases.
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