A short review of human gamma-globin gene anomalies

Abstract

This paper summarizes various anomalies involving the duplicated gamma-globin genes which are normally arranged as -G gamma-A gamma-. Variations include G gamma----A gamma and A gamma----G gamma replacements; newborn heterozygotes for these anomalies have low G gamma (A gamma A gamma/G gamma A gamma) or high G gamma values (G gamma G gamma/G gamma A gamma). Additional abnormalities include the deletion of one gamma-globin gene (-A gamma-; gamma-thalassemia), gamma-globin gene triplications (G gamma-AG gamma-A gamma; G gamma-G gamma-A gamma) and gamma-globin gene quadruplications (G gamma-G gamma-G gamma-A gamma-); several of these conditions are found in different populations but at low frequencies. In adults, the G gamma to A gamma ratio in the Hb F and often also the Hb F level, are directly related to specific structural characteristics of the chromosome; specific mutations in the promoter sequences 5' to G gamma or to A gamma, for instance, may result in increased G gamma or A gamma chain production with an increase in Hb F levels (nondeletional G gamma- or A gamma-HPFH) or with only modest changes in the total Hb F (normal adults; Swiss-HPFH). Similar variations have been observed in SS patients.