Mitochondrial DNA polymorphism in substantia nigra

Robert M.I. Kapsa, M. J.Bernadette Jean-Francois, Patcharee Lertrit, Shan Weng, Nurjati Siregar, Joseline Ojaimi, Geoffrey Donnan, Colin Masters, Edward Byrne

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22 Citations (Scopus)


Inefficiencies in mitochondrial respiration mainly affecting complex I and IV activities, occur with increasing age and have been suggested as a possible etiological factor in age-related neurodegenerative diseases. It has been suggested that this finding may be explained by an accumulation of mtDNA mutations. We hypothesise that some polymorphic mitochondrial genomes encode less efficient respiratory protein subunits and are therefore less tolerant of acquired mutations. If this hypothesis is correct, individuals with 'less efficient' mtDNA genotypes may be predisposed both to more rapid biological aging and to neurodegenerative disease. In this study we investigate the substantia nigra mtDNA composition from 4 elderly individuals (2 non-parkinsonian and 2 with idiopathic Parkinson's disease) to determine whether there is sufficient polymorphism to account for different possible respiratory efficiencies. The mitochondrial tRNA(Arg), tRNA(His), tRNA(Ser), tRNA(Leu(CUN)), ND4L, ND4 and ND5 genes as well as parts of the ND3 and ND6 subunit coding regions were analysed (4221 bp), revealing the presence of multiple deletions and 48 discrete polymorphic sites. These included 23 missense, two tRNA and one nonsense polymorphism. Eight of the missense polymorphisms caused nonconservative amino acid replacements at sites of moderate to high evolutionary constraint. These findings suggest that mtDNA diversity in the ageing brain may account for a range of bioenergetic outcomes. The variation in mtDNA genotype involves both inherited (fixed familial) polymorphism and superimposed acquired mutations.

Original languageEnglish
Pages (from-to)204-211
Number of pages8
JournalJournal of the Neurological Sciences
Issue number1-2
Publication statusPublished - Dec 1996


  • DNA sequencing
  • Parkinson's disease
  • complex I
  • long PCR
  • mitochondrial DNA
  • mtDNA deletion
  • mtDNA polymorphism
  • sequence divergence
  • substantia nigra


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