Mitochondrial DNA and genetic disease.

Since the human mitochondrial genome was characterised and sequenced in 1981, it has been viewed as the likely site of genetic diseases showing a maternal inheritance pattern and associated with defects of the respiratory chain, such as the mitochondrial myopathies (MMs). The properties that make it a candidate for the source of such conditions are that it encodes polypeptides involved in electron transport and that it is maternally inherited. However, several of the mtDNA diseases only fulfill one or other of these criteria: the first group of mtDNA diseases showed only sporadic deletions, and the first point mutation in Leber's Hereditary Optic Neuropathy (LHON) is not associated with a clear biochemical defect. Furthermore, it is now clear that both autosomal dominant and probably recessive nuclear genes can cause abnormalities of mtDNA. Each of these major groups will be considered in turn.