A Novel Mechanism Generating Short Deletion/Insertions Following Slippage is Suggested by a Mutation in the Human α2-Globin Gene

A novel mechanism generating short deletion/insertions is described based on a mutation in the human α2-globin gene. A deletion of 9 bp (codons 39–41) is replaced by an eight nucleotide insertion, duplicating the adjacent downstream sequence. We propose that the mutation arose by slipped strand mispairing (SSM), creating a single-stranded loop, followed by DNA elongation, strand breathing and the formation of a mismatch bubble. An extensive literature search has revealed six additional deletion/insertion mutations in humans in which the inserted nucleotides come from the same DNA strand. Our model explains all six mutations, suggesting that rearrangement of a mismatch loop or bubble during DNA replication may be not uncommon.