Skewed segregation of the mtDNA nt 8993 (T-->G) mutation in human oocytes.
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.
Blok
R B
RB
Murdoch Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
Gook
D A
DA
Thorburn
D R
DR
Dahl
H H
HH
D015925:Cryopreservation; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008957:Models, Genetic; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D009866:Oogenesis; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial