Low "penetrance" of phylogenetic knowledge in mitochondrial disease studies

Biochem Biophys Res Commun. 2005 Jul 22;333(1):122-30. doi: 10.1016/j.bbrc.2005.04.055.


An up-to-date view of the worldwide mitochondrial DNA (mtDNA) phylogeny together with an evaluation of the conservation of each site is a reliable tool for detecting errors in mtDNA studies and assessing the functional importance of alleged pathogenic mutations. However, most of the published studies on mitochondrial diseases make very little use of the phylogenetic knowledge that is currently available. This drawback has two inadvertent consequences: first, there is no sufficient a posteriori quality assessment of complete mtDNA sequencing efforts; and second, no feedback is provided for the general mtDNA database when apparently new mtDNA lineages are discovered. We demonstrate, by way of example, these issues by reanalysing three mtDNA sequencing attempts, two from Europe and another one from East Asia. To further validate our phylogenetic deductions, we completely sequenced two mtDNAs from healthy subjects that nearly match the mtDNAs of two patients, whose sequences gave problematic results.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artifacts*
  • Base Sequence
  • China
  • DNA Mutational Analysis / methods*
  • DNA, Mitochondrial
  • Databases, Genetic*
  • Documentation / methods
  • Epidemiologic Studies
  • European Union
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Testing / methods
  • Genetics, Population / methods*
  • Humans
  • Incidence
  • Mitochondrial Diseases / epidemiology*
  • Mitochondrial Diseases / genetics*
  • Molecular Sequence Data
  • Penetrance
  • Phylogeny*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*


  • DNA, Mitochondrial

Associated data

  • GENBANK/AY963586
  • GENBANK/AY972053