Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study.

Goto H, Dickins B, Afgan E, Paul IM, Taylor J, Makova KD, and Nekrutenko A.
Genome Biology. June 2011; 12:R59
Links: Article at Genome Biology


Originally believed to be a rare phenomenon, heteroplasmy is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies, which are defined as the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue or individual, can be used as genetic markers in applications ranging from forensics to cancer diagnostics. As the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis, it is of critical importance to investigate the dynamics of maternal mtDNA transmission.


In this study, we sequenced mtDNA at high coverage from blood and buccal tissue of nine individuals from three families with a total of six maternal transmission events. Using simulations and re-sequencing of clonal DNA, we devised a set of criteria for detecting polymorphic sites in heterogeneous genetic samples that is resistant to the noise originating from massively parallel sequencing technologies. Application of these criteria to nine human mtDNA samples revealed four heteroplasmic sites.


Our results suggest that the incidence of heteroplasmy may be lower than estimated in some other recent re-sequencing studies, and that mtDNA allelic frequencies differ significantly both between tissues of the same individual and between a mother and her offspring. We designed our study in such a way that the complete analysis can be repeated by anyone either at our Galaxy website or directly on the Amazon Cloud. Our computational pipeline can be easily modified to accommodate other applications, such as viral re-sequencing.