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Evidence that two reports of mtDNA cytochrome c oxidase "mutations" in Alzheimer's disease are based on nDNA pseudogenes of recent evolutionary origin.

Abstract：

:Recently, two reports [R. E. Davis et al. (1997) Proc. Natl. Acad. Sci. USA 94, 4564-4569 and E. Fahy et al. (1997) Nucleic Acids Res. 25, 3102-3109] described a series of heteroplasmic mitochondrial DNA (mtDNA) mutations in the genes encoding two cytochrome c oxidase subunits (CO1 and CO2) which segregated in higher abundance with Alzheimer's disease subjects than controls. Using mtDNA-depleted NT2 cells, we provide further evidence that these two reports are erroneously based on a PCR artifact arising from the amplification of nuclear DNA encoded mtDNA pseudogenes (mtDNA psi s). Our findings are similar, but not identical, to other recent studies of these putative mtDNA psi sequences. This sequence variability may indicate that multiple mtDNA psi s, all of comparatively recent evolutionary origin are involved. While such pseudogenes are interesting in that they provide a molecular evolutionary "snapshot" of human ancestral mtDNA, it is unlikely that they play any role in the etiology of Alzheimer's disease.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Davis JN 2nd,Parker WD Jr

doi

10.1006/bbrc.1998.8353

subject

Has Abstract

pub_date

1998-03-27 00:00:00

pages

877-83

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98353-X

journal_volume

244

pub_type

杂志文章

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