It is now clear that molecular defects in human mitochondrial DNA play a 
significant role in human disease. Mitochondrial DNA mutations range from single 
base changes in the 16.5 kilobase-pair genome up to large deletions and 
rearrangements. Independently of the actual cause of a given mutation, it is 
possible to predict at least some of the consequences of changes in 
mitochondrial DNA sequence. This paper reviews our overall understanding of the 
mode and mechanism of mitochondrial DNA replication and transcription and how 
this relates to mitochondrial gene expression. This provides a background to 
anticipate the nature and extent of mitochondrial DNA sequence changes that 
might be of physiological consequence.