THE IN-VIVO EXPRESSION OF THE GLOBIN GENES OF THE BETA CISTRON IN GAMMA-THALASSEMIA, DELTA-THALASSEMIA, AND DELTA-BETA-THALASSEMIA HETEROZYGOTES

There is considerable evidence suggesting that the switch from gamma t o delta and beta chain production after birth is due, in part, to sile ncing of the gamma genes by stage-specific factors which bind to their promoters and to the competition from the adult (delta and beta) gene s for a common enhancer element located in the locus control region. A s a consequence one can expect that the increased Hb F production in a dults with hereditary persistence of fetal hemoglobin or delta beta-th alassemia is directed mainly by gamma-globin genes in cis to the delet ion(s) responsible for these conditions. Here we review data on hetero zygotes with gamma-, delta- or delta beta-thalassemia, who also had an (A) gamma(T) mutation, in cis or in trans, which was used as a marker of gamma gene expression. The results show that a deletion affecting adult beta genes favors the expression of gamma genes in cis, while th e deletion of a single gamma gene does not affect the expression of th e beta gene in cis but leads to a faster gamma --> beta switch postnat ally.