Two direct repeats cause most human mtDNA deletions

Mitochondrial DNA (mtDNA) deletions are a common cause of human mitochondrial disease and also occur as part of normal aging. However, it is unknown how the deletions actually occur. To gain further insight, we studied the sequences that flank 263 different human mtDNA deletions. The distribution of deletion breakpoints did not correspond to the basic parameters of wild-type mtDNA that are thought to predispose to deletion formation. But there was a striking correspondence to the position of two 13-bp direct repeats beginning at nucleotides 8470 and 13447. The vast majority of different mtDNA deletions appear to be related to these two repeats, suggesting a common mechanism related to mtDNA replication.