Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA

The frequency of intraindividual mitochondrial DNA (mtDNA) polymorphisms—heteroplasmies—can change dramatically from mother to child owing to the mitochondrial bottleneck at oogenesis. For deleterious heteroplasmies such a change may transform alleles that are benign at low frequency in a mother into disease-causing alleles when at a high frequency in her child. Our study estimates the mtDNA germ-line bottleneck to be small (30-35) and documents a positive association between the number of child heteroplasmies and maternal age at fertilization, enabling prediction of transmission of disease-causing variants and informing mtDNA evolution.