title: Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.
abstract: In an unprecedented finding, Davis et al. [Davis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N. & Parker, W. D., Jr. (1997) Proc. Natl. Acad. Sci. USA 94, 4526-4531] used an unusual DNA isolation method to show that healthy adults harbor a specific population of mutated mitochondrial cytochrome c oxidase (COX) genes that coexist with normal mtDNAs. They reported that this heteroplasmic population was present at a level of 10-15% in the blood of normal individuals and at a significantly higher level (20-30%) in patients with sporadic Alzheimer's disease. We provide compelling evidence that the DNA isolation method employed resulted in the coamplification of authentic mtDNA-encoded COX genes together with highly similar COX-like sequences embedded in nuclear DNA ("mtDNA pseudogenes"). We conclude that the observed heteroplasmy is an artifact.
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. mh29@columbia.edu
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: A
authors.initials: A
authors.lastname: Shtilbans
authors.forename: R
authors.initials: R
authors.lastname: Mayeux
authors.forename: M M
authors.initials: MM
authors.lastname: Davidson
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D011544:Pseudogenes
chemical_list: D004272:DNA, Mitochondrial