Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency

Maria Ximena Sosa, I. K.Ashok Sivakumar, Samantha Maragh, Vamsi Veeramachaneni, Ramesh Hariharan, Minothi Parulekar, Karin M. Fredrikson, Timothy T. Harkins, Jeffrey Lin, Andrew B. Feldman, Pramila Tata, Georg B. Ehret, Aravinda Chakravarti

Research output: Contribution to journalArticlepeer-review


We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10-4, nucleotide diversity of 1.6×10-3 for CEU and 3.7×10-3 for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine.

Original languageEnglish (US)
Article numbere1002737
JournalPLoS computational biology
Issue number10
StatePublished - Oct 2012
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics


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