Skewed segregation of the mtDNA nt 8993 (T-->G) mutation in human oocytes

Am J Hum Genet. 1997 Jun;60(6):1495-501. doi: 10.1086/515453.


Rapid changes in mtDNA variants between generations have led to the bottleneck theory, which proposes a dramatic reduction in mtDNA numbers during early oogenesis. We studied oocytes from a woman with heteroplasmic expression of the mtDNA nt 8993 (T-->G) mutation. Of seven oocytes analyzed, one showed no evidence of the mutation, and the remaining six had a mutant load > 95%. This skewed expression of the mutation in oocytes is not compatible with the conventional bottleneck theory. A possible explanation is that, during amplification of mtDNA in the developing oocyte, mtDNA from one mitochondrion is preferentially amplified. Thus, subsequent mature oocytes may contain predominantly wild-type or mutant mitochondrial genomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryopreservation
  • DNA, Mitochondrial / biosynthesis
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Amplification
  • Genomic Imprinting
  • Humans
  • Male
  • Mitochondria / metabolism
  • Models, Genetic*
  • Oocytes / cytology
  • Oocytes / physiology*
  • Oogenesis
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction


  • DNA, Mitochondrial