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PMID: 9405710 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 26 ·1997-12-23 ·Pages 14894-9

Hirano M, Shtilbans A, Mayeux R, Davidson MM, DiMauro S, Knowles JA, Schon EA

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.

MeSH Terms
Adult Alzheimer Disease/genetics Cell Nucleus/genetics DNA, Mitochondrial/genetics Humans Polymerase Chain Reaction Pseudogenes
Chemicals
DNA, Mitochondrial
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hirano M
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. mh29@columbia.edu
Shtilbans A
Mayeux R
Davidson M M
DiMauro S
Knowles J A
Schon E A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.26.14894
Email
mh29@columbia.edu
Published
1997-12-23
Pages
14894-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC25134
Subset
IM
Grants
NINDS NIH HHS · NS11766 · United States
NCRR NIH HHS · M01 RR000645 · United States
NIA NIH HHS · P50 AG008702 · United States
NINDS NIH HHS · NS01617 · United States
NIA NIH HHS · P01 AG007232 · United States
NINDS NIH HHS · NS28828 · United States
NINDS NIH HHS · P01 NS011766 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.26.14894 PMC Full Text View journal details
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