Large scale mtDNA sequencing reveals sequence and functional conservation as major determinants of homoplasmic mtDNA variant distribution

A. M. Voets, B. J. C. van den Bosch, A. P. Stassen, A. T. Hendrickx, D. M. Hellebrekers, Lut Van Laer, E Van Eyken, P.G. Camp, Angela Pyle, S. V. Baudouin, Patrick F Chinnery, H. J. M. Smeets*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all.
Original languageEnglish
Pages (from-to)964-972
Issue number6
Publication statusPublished - Nov 2011


  • MitoChip
  • mtDNA variants
  • Distribution
  • Pathogenicity

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