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

The human nuclear gene (POLG) for the catalytic subunit of mitochondrial DN A polymerase (DNA polymerase gamma) contains a trinucleotide CAG microsatel lite repeat within the coding sequence, We have investigated the frequency of different repeat-length alleles in populations of diseased and healthy i ndividuals, The predominant allele of 10 CAG repeats was found at a very si milar frequency (approximately 88%) in both Finnish and ethnically mixed po pulation samples,,vith homozygosity close to the equilibrium prediction, Ot her alleles of between 5 and 13 repeat units were detected, but no larger, expanded alleles were found, A series of 51 British myotonic dystrophy pati ents showed no significant variation from controls, indicating an absence o f generalised CAG repeat instability, Patients,vith a variety of molecular lesions in mtDNA, including sporadic, clonal deletions, maternally inherite d point mutations, autosomally transmitted mtDNA depletion and autosomal do minant multiple deletions showed no differences in POLG trinucleotide repea t-length distribution from controls, These findings rule out POLG repeat ex pansion as a common pathogenic mechanism in disorders characterised by mito chondrial genome instability.