title: Analysis of the trinucleotide CAG repeat from the human mitochondrial DNA polymerase gene in healthy and diseased individuals.
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.
authors: Institute of Medical Technology, University of Tampere, Finland.
authors: A
authors: A
authors: Rovio
authors: V
authors: V
authors: Tiranti
authors: A L
authors: AL
authors: Bednarz
authors: A
authors: A
authors: Suomalainen
authors: J N
authors: JN
authors: Spelbrink
authors: N
authors: N
authors: Lecrenier
authors: A
authors: A
authors: Melberg
authors: M
authors: M
authors: Zeviani
authors: J
authors: J
authors: Poulton
authors: F
authors: F
authors: Foury
authors: H T
authors: HT
authors: Jacobs
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D000074002:DNA Polymerase gamma; D018076:DNA, Complementary; D004272:DNA, Mitochondrial; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D018911:Trinucleotide Repeats
chemical_list: D018076:DNA, Complementary; D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase