Assessing mitochondrial heteroplasmy using next generation sequencing: A note of caution

Mitochondrion. 2019 May:46:302-306. doi: 10.1016/j.mito.2018.08.003. Epub 2018 Aug 9.

Abstract

The mitochondrial genome has recently become the focus of several high-impact next-generation sequencing studies investigating the effect of mutations in disease and assessing the efficacy of mitochondrial replacement therapies. However, these studies have failed to take into consideration the capture of recurring translocations of mitochondrial DNA to the nuclear genome, known as nuclear mitochondrial sequences (NUMTs), continuing to align sequence data to the revised Cambridge reference sequence alone. Here, using different mtDNA enrichment techniques and a variety of tissues, we demonstrate that NUMTs are present in sequence data and that, dependent upon downstream analysis, are at a level which affects variant calling.

Keywords: Bioinformatic analysis; Heteroplasmy; Mitochondrial DNA; Next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • DNA, Mitochondrial / genetics*
  • Genetic Variation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics*
  • Sequence Analysis, DNA

Substances

  • DNA, Mitochondrial