Occurrence of a particular base substitution (3243 A to G) in mitochondrial DNA of tissues of ageing humans.

Allele-specific polymerase chain reaction has been used to demonstrate the occurrence, during the human ageing process, of the mutation A to G at nucleotide position 3243 on mitochondrial DNA. An oligonucleotide with a 3'-end specific to this mutation was designed to selectively amplify DNA bearing this mutation under annealing temperature conditions that efficiently discriminate between normal and mutant mitochondrial DNA templates. Seven out of 38 adult tissues tested were found to contain this mutation, whereas the mutation could not be detected in any of the 16 infant tissues analyzed. The present demonstration of an age-related point mutation adds to the growing list of mutations in human mitochondrial DNA, till now almost exclusively large deletions, that accumulate in human tissues as a function of age. The method described here has general application in the detection of other age-related point mutations in human mitochondrial DNA.