Profiling of mitochondrial genomes in SCA3/MJD patients from mainland China.

Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), is the most common type of autosomal dominant cerebellar ataxias. Few studies focused on the changes of the whole mitochondrial genomes of SCA3/MJD patients and its relationship with the pathogenesis of SCA3/MJD. We adapted one-step long-range PCR to amplify the entire mitochondrial DNA (mtDNA) followed by next-generation sequencing technology to investigate the information of whole mitochondrial genomes in 38 SCA3/MJD patients and 31 healthy controls from mainland China. Compared to the healthy control group, the mitochondrial variations in SCA3/MJD patients were more concentrated in the tRNA-transcribed genes which were further found to be potentially associated with the pathogenesis of SCA3/MJD by SKAT-O analysis. However, owning variations in tRNA-transcribed genes could not affect the age of onset (AO) of SCA3/MJD patients. We also noticed that the variant loads greater than 90% took up more in SCA3/MJD patients than in controls. Moreover, from our preliminary study, compared to the patients whose ages of onset were elder than 20, the mitochondrial genomes showed no difference in those AO less than 20. This is the first study to demonstrate the feasibility of using the next-generation sequencing technology for mtDNA variant analysis of SCA3/MJD patients from mainland China. And this research enriches the genetic information of SCA3/MJD and provides a direction for further investigations about the mitochondrial genomes in SCA3/MJD.