STRUCTURAL CHARACTERIZATION OF THE BETA-GLOBIN GENE-CLUSTER IN AN INDIVIDUAL EXPRESSING A VERY-LOW LEVEL OF (G)GAMMA GLOBIN CHAINS

We report the case of a normal individual displaying an extremely unba lanced (G) gamma/(A) gamma-globin ratio ((G) gamma-globin chains undet ectable by urea/triton/ acrylamide gel electrophoresis and just reachi ng the threshold of detection by high performance liquid chromatograph y) associated with a very low level of (G) gamma-globin mRNA (at the m ost 5% of total gamma-mRNA after reverse transcriptase polymerase chai n reaction determination). By DNA Southern blotting and sequencing, th e very low level of (G) gamma-globin chains in this individual was fou nd in association with subhaplotype [+ - - - - -] (Hinc II 5' to epsil on, Xmn I 5' to (G) gamma, Hind III in (G) gamma and (A) gamma, Hinc I I in and 3' to psi beta), with (G) gamma- and (A) gamma-globlin gene s equences of the B type chromosome, and with a number of AT repeats in the locus control region hypersensitive site-2 site, similar to that r eported to be associated with the Bantu beta(S) haplotype. These struc tural characteristics, described for the first time combined in the sa me individual, suggest that the (G) gamma/(A) gamma ratio in adults, i s controlled by sequences distributed all along the beta-globin gene c luster.