Deep sequencing of mitochondrial genomes reveals increased mutation load in Friedreich's ataxia.

ABSTRACT:

Objective

Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat expansion disorder caused by epigenetic silencing of the frataxin gene (FXN). Current research suggests that damage and variation of mitochondrial DNA (mtDNA) contribute to the molecular pathogenesis of FRDA. We sought to establish the extent of the mutation burden across the mitochondrial genome in FRDA cells and investigate the molecular mechanisms connecting FXN downregulation and the acquisition of mtDNA damage.

Methods

Damage and mutation load in mtDNA of a panel of FRDA and control fibroblasts were determined using qPCR and next-generation MiSeq sequencing, respectively. The capacity of FRDA and control cells to repair oxidative lesions in their mtDNA was measured using a quantitative D

SUBMITTER: Bhalla AD 

PROVIDER: S-EPMC4931717 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature