A maternal line study investigating the 4977-bp mitochondrial DNA deletion

The most frequently reported species of mitochondrial DNA (mtDNA) damage associated with ageing is the 4977-bp 'Common Deletion'. However, recent observations have raised several issues within the deletion debate namely: the significance of the 4977-bp deletion (CD) as a universal DNA marker of ageing and mitochondrial dysfunction; and the possibility for maternal transmission of deletions in humans. Previous attempts at answering these questions have been limited because many investigations have been cross-sectional studies of unrelated individuals. With the unique feature of the maternal inheritance of mtDNA, our study overcomes some of these limitations by investigating the CD in human maternal lines, which represent 21 families spanning four generations. Using a highly sensitive PCR methodology, we identified the presence of the CD in leukocytes from all 71 individuals (age range-8 months-99 years) including all infants and children (n=15) which in addition were free of any known mitochondrial diseases. This is important because the few reports of the CD in infants have been linked to mitochondrial disease. These results question the significance of the CD as a universal DNA marker of ageing and subsequent mitochondrial dysfunction and provide support for the possibility for maternal transmission of deletions.