Our aim is to study low-level heteroplasmy in a large number of mother-child pairs using DNA samples already extracted for ALSPAC genotyping studies. We estimate that greater than 1000 pairs will be required to carry out a meaningful experiment, based on our pilot data from existing data sets. We will use ultra high depth next generation sequencing (IlluminaMiSeq) to carry out this experiment, allowing the detection of greater than 0.5% heteroplasmy from a standard genomic DNA sample. Statistical analysis will be carried out by Dr Ian Wilson at the Institute of Genetic Medicine. We will model the genetic bottleneck as done previously,7 and determine whether the background mtDNA sequence influences the rate of segregation of mtDNA heteroplasmy in healthy controls. We will then compare this to data acquired from humans transmitting pathogenic mtDNA mutations to determine whether they behave differently.8 This will advance our understanding of the underlying biology, and will be directly relevant to current work aimed at preventing the transmission of mtDNA mutations.