Mitochondrial heteroplasmy among maternally related individuals

The second hypervariable segment of the human mtDNA control region contains a homopolymeric tract of cytidines between nucleotides (nt) 303 and 315, interrupted by a thymidine at position 310, according to the Cambridge reference sequence. By direct sequencing, some individuals show blurred sequence chromatograms in this region which are not caused by a sequencing artefact but by high levels of length heteroplasmy. With respect to this length heteroplasmy ten maternally related individuals and two unrelated probands were examined. The relative proportions of length variants in the homopolymeric tract in selected individuals were determined by cloning and sequencing of multiple independent clones. All ten family members examined were heteroplasmic while the proportions of each genotype varied widely in different individuals. The size of a possible mitochondrial bottleneck during embryonic development of the offspring is discussed with respect to the changes in mitochondrial haplotypes within mother-offspring pairs. Our data are consistent with both slow and rapid segregation of mtDNAs between the generations, which would implicate a tight as well as a wide bottleneck. Therefore, a common bottleneck size in all individuals from this lineage seems to be very unlikely.