Objective: To understand the mutational patterns and mechanism of short tandem repeats(STRs).
Methods: The DNA samples of 19 parent-child pairs with mutations in three loci (FGA, D12S391, and D11S554) were genotyped by silver staining on STR. Alleles to be sequenced were excised from gels, reamplified by PCR, and purified. Sequencing was performed by use of cycle sequencing.
Results: There were 18 out of 19 pedigrees in which the 'new' alleles gained or lost a single repeat (8 gains, 7 losses, and 3 being indistinguishable). Only one pedigree lost two repeats. In the 19 pedigrees, there were 13 pedigrees whose 'new' alleles came from fathers, 3 from mothers, 3 from either father or mother. The ratio was 4 1 between fathers and mothers. The mutation of three STR loci occurred in the long, uninterrupted tetranucleotide repeat regions ('CTTT' in FGA, 'AGAT' in D12S391, and 'AAAG' in D11S554).
Conclusion: Single- step mutations accounted for 95% of STR mutation events in these three loci: FGA, D12S391, and D11S554. The rest were double step mutations. There was no insertion or deletion of an incomplete repeat in any of the pedigrees. The mutation was mainly caused by fathers. The long, uninterrupted tetranucleotide repeats in these three loci might be susceptible to mutation.