Multiple mitochondrial DNA deletions in an elderly human individual

Abstract

We have used the polymerase chain reaction (PCR) to study deletions in the mitochondrial DNA (mtDNA) of an elderly human individual, An extended set of PCR primers has been utilised to identify 10 mitochondrial DNA deletions in a 69-year-old female subject with no known mitochondrial disease. The particular deletions visualised as PCR products depended on the primer pairs used, such that the more distantly separated PCR primers enabled visualisation of larger deletions. Some deletions were common to the heart, brain and skeletal muscle, whereas others were apparently specific to individual tissues. DNA sequencing analysis of PCR products showed that short direct repeat sequences (5 to 13 bp) flanked all deletion breakpoints; in most cases one copy of the repeat was deleted, It is proposed that the accumulation of such multiple deletions is a general phenomenon during the ageing process.

Prevalence of 4977bp Deletion in Mitochondrial DNA from Patients with Chronic Kidney Disease Receiving Conservative Treatment or Hemodialysis in Southern Brazil

“…As each cell contains multiple mtDNA molecules, normal and mtDNA 4977bp deletion can coexist in the same cell, a condition known as heteroplasmy. [29][30][31] Our results agreed with those of Zhang et al, [31] showing that it is possible to detect a specific mutant fragment generated by the deletion of 4977bp in mtDNA with a single primer pair. In this study, 100ng of total DNA in each sample were sufficient to detect the 160bp fragment generated by the mtDNA 4977bp deletion.…”

Morpho-dynamic changes of mitochondria during ageing of human endothelial cells

“…Semiquantitative PCR revealed a significant loss of intact mtDNA. Although we did not check for the typical deletions common in ageing cells, the PCR amplification product of the mtDNA genome (5999-14882) encompasses the region where many deletions occur (Trounce et al, 1989;Katayama et al, 1991;Zhang et al, 1992). To our knowledge, this is the first study showing this kind of changes in the mtDNA of HUVEC cells during ageing.…”

Very Rare Complementation between Mitochondria Carrying Different Mitochondrial DNA Mutations Points to Intrinsic Genetic Autonomy of the Organelles in Cultured Human Cells

“…Another area where the observed tendency of mammalian mitochondria to remain genetically autonomous has significant implications is that of aging-dependent mtDNA damage. There is substantial evidence of an aging-related occurrence in mtDNA of oxidative derivatives of nucleotides (50), of small deletions and insertions, and of large deletions (51)(52)(53)(54). Most significantly, very recently an aging-dependent large accumulation of specific mutations in a critical control region for mtDNA replication has been demonstrated in human fibroblasts (55).…”