Normal Δ-Globin Gene Sequences in Sardinian Nondeletional Δβ-Thalassemia

Abstract

In order to clarify the reasons for the reduced Hb A₂ levels in Sardinian δβ-thalassemia, we characterized, both by cloning and sequence analysis and by direct sequencing of amplified DNA, the δ-globin gene from an individual of Sardinian descent who is a compound heterozygote for the β β-thalassemia codon 39 (C→T) nonsense mutation and the Sardinian δβ-thalassemia [codon 39(C→T)/ -196(C→T)A_γ]. The analysis of the δ-globin gene from the δβ-thal-assemia chromosome revealed an entirely normal sequence. The defective function of the δ-globin gene in this determinant is thus likely related to a suppressive effect of the in cis nondele-tional high persistence of fetal hemoglobin mutation of the A_γ gene, probably resulting from an increased capability of the relative promoter to interact with the locus control region.