Background Huntington’s disease (HD) is a neurodegenerative disorder that runs in families. The gene for HD has been identified several years ago however the biology of the illness itself is still poorly understood. Chromosomes which are the physical units of genetic information are protected from fraying in successive cell divisions by repetitive sequences called telomeres. Telomere shortening is related to premature cellular senescence and could be a marker for cellular pathology in neurological diseases.
Aims We will estimate telomere length and mitochondrial DNA copy number in blood cells from HD patients. We will also estimate cell cycle patterns and mitochondrial function in HD patient derived cell lines.
Methods Patients and unaffected individuals are recruited after obtaining informed consent. Genomic DNA is isolated from blood of individuals. The isolated genomic DNA is used for estimation of CAG repeat number in the Huntingtin gene. Real time PCR is carried out to estimate telomere length and mitochondrial copy number. PBMCs are transformed using EBV virus to make lymphoblastoid lines(LCLs) from patient blood. Indicator dyes are used with fluorescence activated cell sorting to estimate cell cycle and mitochondrial parameters.
Results and conclusions Our experiments on telomere length estimation showed that there was telomere attrition in neurodegenerative disorders compared to age matched controls. Individuals with HD had the lowest relative telomere copy/single copy gene ratio (0.21), followed by ataxia telangiectasia (0.31) and dementia (0.48). The reduced telomere length could be indicative of shared biological pathways across these disorders contributing to cellular senescence. LCLs have been created from eight patients with different CAG repeat lengths using EBV. Data obtained from the realtime and FACS experiments will be presented and discussed.
- Huntingtons disease
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