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