Segregation of mitochondrial genomes in a heteroplasmic lineage with Leber hereditary optic neuroretinopathy.

Relatively little is known about the factors maintaining mitochondrial DNA (mtDNA) sequence diversity in humans. A detailed understanding of the transmission genetics of mtDNA has been partly hampered by the lack of evidence for heteroplasmic individuals. Among families with Leber hereditary optic neuroretinopathy, we found a maternal lineage with individuals heteroplasmic for a single nucleotide change, and we were able to follow the segregation of polymorphic mitochondrial genomes over 3 generations. The results show that rapid segregation can occur but also that the level of heteroplasmy can be maintained from one generation to another. In this family the disease phenotype is associated with the mtDNA sequence change, confirming the involvement of the mutation in the disease.