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.
Applied Bio-molecular Science Program, Lakehead University, 310 1294 Balmoral Street, Thunder Bay, Ont., Canada P7B 5Z5. robert.thayer@genesisgenomics.com
Robert E
RE
Thayer
Roy
R
Wittock
Ryan
R
Parr
Steve
S
Zullo
Mark A
MA
Birch-Machin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000502:physiology; D008875:Middle Aged; D009035:Mothers; D016133:Polymerase Chain Reaction / Q000379:methods
D017931:DNA Primers; D004272:DNA, Mitochondrial