Analysis of the trinucleotide CAG repeat from the human mitochondrial DNA polymerase gene in healthy and diseased individuals.

TitleAnalysis of the trinucleotide CAG repeat from the human mitochondrial DNA polymerase gene in healthy and diseased individuals.
Publication TypeJournal Article
Year of Publication1999
AuthorsRovio, A, Tiranti, V, Bednarz, AL, Suomalainen, A, Spelbrink, JN, Lecrenier, N, Melberg, A, Zeviani, M, Poulton, J, Foury, F, Jacobs, HT
JournalEur J Hum Genet
Volume7
Issue2
Pagination140-6
Date Published1999 Feb-Mar
ISSN1018-4813
KeywordsAlleles, Amino Acid Sequence, Base Sequence, DNA Polymerase gamma, DNA, Complementary, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Humans, Mitochondria, Molecular Sequence Data, Trinucleotide Repeats
Abstract

The human nuclear gene (POLG) for the catalytic subunit of mitochondrial DNA polymerase (DNA polymerase gamma) contains a trinucleotide CAG microsatellite repeat within the coding sequence. We have investigated the frequency of different repeat-length alleles in populations of diseased and healthy individuals. The predominant allele of 10 CAG repeats was found at a very similar frequency (approximately 88%) in both Finnish and ethnically mixed population samples, with homozygosity close to the equilibrium prediction. Other alleles of between 5 and 13 repeat units were detected, but no larger, expanded alleles were found. A series of 51 British myotonic dystrophy patients showed no significant variation from controls, indicating an absence of generalised CAG repeat instability. Patients with a variety of molecular lesions in mtDNA, including sporadic, clonal deletions, maternally inherited point mutations, autosomally transmitted mtDNA depletion and autosomal dominant multiple deletions showed no differences in POLG trinucleotide repeat-length distribution from controls. These findings rule out POLG repeat expansion as a common pathogenic mechanism in disorders characterised by mitochondrial genome instability.

DOI10.1038/sj.ejhg.5200244
Alternate JournalEur. J. Hum. Genet.
Citation Key10.1038/sj.ejhg.5200244
PubMed ID10196696
Grant List / / Wellcome Trust / United Kingdom