Multiple deletions of mtDNA remove the light strand origin of replication

Idiopathic inflammatory myopathies are progressive, debilitating muscle dis eases. The pathogenesis of these disorders is multifactorial and appears to include mutations of the mitochondrial genome, which are usually indicated by morphological changes of mitochondria. The vast majority of all mitocho ndrial DNA deletions found are located between the origins of replication i n the "major region" between nt5760-nt190. Using long distance PCR and sequ encing techniques, me detected deletions which were unusually large (ca. 10 500-12800 bp) and show uncommon 5'-breakpoints between nt800 and nt3326. Un like most other deletions, their breakpoints are far upstream of the "major region." The atypical location of these deletions suggests a different pat homechanism. The impact of the mitochondrial DNA deletions in the pathogene tic cascade remains uncertain. (C) 2000 Academic Press.