title: Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA.
abstract: Large-scale deletions of mitochondrial DNA (mtDNA) have been described in patients with progressive external ophthalmoplegia (PEO) and ragged red fibers. We have determined the exact deletion breakpoint in 28 cases with PEO, including 12 patients already shown to harbor an identical deletion; the other patients had 16 different deletions. The deletions fell into two classes. In Class I (9 deletions; 71% of the patients), the deletion was flanked by perfect direct repeats, located (in normal mtDNA) at the edges of the deletion. In Class II (8 deletions; 29% of patients), the deletions were not flanked by any obviously unique repeat element, or they were flanked by repeat elements which were located imprecisely relative to the breakpoints. Computer analysis showed a correlation between the location of the deletion breakpoints and sequences in human mtDNA similar to the target sequence for Drosophila topoisomerase II. It is not known how these deletions originate, but both slipped mispairing and legitimate recombination could be mechanisms playing a major role in the generation of the large mtDNA deletions found in PEO.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
authors.forename: S
authors.initials: S
authors.lastname: Mita
authors.forename: R
authors.initials: R
authors.lastname: Rizzuto
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: E
authors.initials: E
authors.lastname: Arnaudo
authors.forename: G M
authors.initials: GM
authors.lastname: Fabrizi
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D003201:Computers; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004272:DNA, Mitochondrial