Structural Characterization of the β-Globin Gene Cluster in An Individual Expressing A Very Low Ll of ^Gγ Globin Chains

Abstract

We report the case of a normal individual displaying an extremely unbalanced ^Gγ/^Aγ-globin ratio (^Gγ-globin chains undetectable by urea/triton/ acrylamide gel electrophoresis and just reaching the threshold of detection by high performance liquid chromatography) associated with a very low level of ^Gγ-globin mRNA (at the most 5% of total γ-mRNA after reverse transcriptase polymerase chain reaction determination). By DNA Southern blotting and sequencing, the very low level of ^Gγ-globin chains in this individual was found in association with subhaplotype [+ - — -] (Hinc II 5′ to , Xmn I 5′ to ^Gγ, Hind III in ^Gγ and ^Aγ, Hinc II in and 3′ to PSβ), with ^Gγ- and ^Aγ-globin gene sequences of the B type chromosome, and with a number of AT repeats in the locus control region hypersensitive site-2 site, similar to that reported to be associated with the Bantu β^S haplotype. These structural characteristics, described for the first time combined in the same individual, suggest that the ^Gγ/^Aγ ratio in adults, is controlled by sequences distributed all along the β-globin gene cluster.