Figure 1: The generation of embryonic stem cells through in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI) and somatic cell nuclear transfer (SCNT).Following maturation, the oocyte can be fertilised with sperm by either a sperm swimming to an egg and penetrating it (A) or by a sperm being directly injected into the cytoplasm of the egg (ICSI; B). Following these approaches, the resultant embryos will usually possess egg mtDNA only (homoplasmic). For somatic cell nuclear transfer (SCNT; C), the nucleus from a matured egg is removed (enucleated) and replaced with a somatic cell consisting of a nucleus plus other cytoplasmic components such as mitochondria. Consequently, the reconstructed eggs will possess either two populations of mtDNA (heteroplasmy) or recipient egg mtDNA only (homoplasmy). The population of mtDNA present in the embryonic stem cells will be representative of the mtDNA populations present following SCNT but, in the case of heteroplasmy, one population may be preferentially selected for, which could in turn result in homoplasmy. In order to avoid heteroplasmy, the egg’s mitochondrial DNA can be depleted and replaced with a population of mitochondrial DNA that is compatible with the donor cell (D).