Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder

Autism Res. 2017 Aug;10(8):1338-1343. doi: 10.1002/aur.1792. Epub 2017 Apr 17.


Autism is a complex genetic disorder where both de-novo and inherited genetics factors play a role. Next generation sequencing approaches have been extensively used to identify rare variants associated with autism. To date, all such studies were focused on nuclear genome; thereby leaving the role of mitochondrial DNA (mtDNA) variation in autism unexplored. Recently, analytical tools have been developed to evaluate mtDNA in whole-exome data. We have analyzed the mtDNA sequence derived from whole-exome sequencing in 10 multiplex families. In one of the families we have identified two variants of interest in MT-ND5 gene that were previously determined to impair mitochondrial function. In addition in a second family we have identified two VOIs; mtDNA variant in MT-ATP6 and nuclear DNA variant in NDUFS4, where both VOIs are within mitochondrial Respiratory Chain Complex. Our findings provide further support for the role of mitochondria in ASD and confirm that whole-exome sequencing allows for analysis of mtDNA, which sets a stage for further comprehensive genetic investigations of the role of mitochondria in autism. Autism Res 2017, 10: 1338-1343. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Keywords: autism spectrum disorder; mitochondria; next generation sequencing; single nucleotide variation; whole exome sequencing.

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • DNA, Mitochondrial / genetics*
  • Exome / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Registries


  • DNA, Mitochondrial