A novel mechanism generating short deletion/insertions following slippage is suggested by a mutation in the human alpha2-globin gene.
A novel mechanism generating short deletion/insertions is described based on a mutation in the human alpha2-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.
Oron-Karni
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V
Department of Hematology, Hebrew University-Hadassah Medical School, Hadassah University Hospital, Jerusalem, Israel.
Filon
D
D
Rund
D
D
Oppenheim
A
A
D000293:Adolescent; D000328:Adult; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D016254:Mutagenesis, Insertional; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000235:genetics
D005914:Globins