Variations within mitochondrial DNA (mtDNA) sequence give rise to heteroplasmy, defined as the presence of multiple distinct mitochondrial sequences within an individual. Heteroplasmy is a clinically significant state, since the severity of many mitochondrial disorders is dependent upon the ratio between wild-type and mutant sequences, with progressively more severe symptoms emerging as the ratio of mutated to normal genomes rises (1). Indeed, human mitochondrial heteroplasmy was first identified in studies of mitochondrial disease genetics where variable levels of deletions (2) or mutations (3) were noted in affected patients. However, heteroplasmy is not necessarily a pathogenic state. Heteroplasmic variations without apparent functional consequence are observed in samples from populations without overt mitochondrial disease (4). The frequency of heteroplasmy has been estimated in two studies of the hypervariable regions of mtDNA that found that >10% of individuals were heteroplasmic within these regions (5,6). A recent study using deep sequencing of the complete mitochondrial genome found that ∼25% of individuals had a heteroplasmic site across the entire genome (7).