Allele frequency distribution of the (TG)n(AG)m microsatellite in the apolipoprotein C-II gene

The dinucleotide (TG)n interspersed repetitive sequences are the most abundant microsatellites in the human genome. Using the polymerase chain reaction to amplify a (TG)n(AG)m microsatellite in the first intron of the apo C-II gene, we have detected 15 different alleles in 242 unrelated individuals of French ancestry. The heterozygosity index was 0.85 and codominant Mendelian inheritance of the alleles was observed in individuals from 121 nuclear families. We report that polymorphism at this locus is attributable to length variation at both (TG)n and (AG)m motifs, although the (AG)m motif contains only two alleles differing by one repeat unit. A quadrimodal allele frequency distribution was observed at the (TG)n(AG)m locus. Each of the first three modes comprises one frequent allele and one very rare allele adjacent in size. No alleles of intermediate size were found between the three first modes. The fourth mode encompasses nine alleles that span from 27 to 35 repeat units. We suggest that this distribution reflects the molecular mechanisms by which alleles give rise to one another.