Self-catalytic DNA depurination underlies human β-globin gene mutations at codon 6 that cause anemias and thalassemias

Abstract

Background: A self-catalytic depurination sequence centered at codon 6 in the β-globin gene creates a mutagenic apurinic site. Results: Unique codon 6 haplotypes, many anemia- and thalassemia-causing, far exceed haplotypes at other β-globin codons. Conclusion: Excessive mutagenicity at the only β-globin self-depurination site indicates a mechanism discovered in vitro that functions in vivo. Significance: In vivo functionality of self-depurination sites in genes can spontaneously cause diseases via somatic mutations. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.