The in vivo expression of the globin genes of the beta cistron in gamma-, delta-, and delta beta-thalassemia heterozygotes.

There is considerable evidence suggesting that the switch from gamma to delta and beta chain production after birth is due, in part, to silencing of the gamma genes by stage-specific factors which bind to their promoters and to the competition from the adult (delta and beta) genes for a common enhancer element located in the locus control region. As a consequence one can expect that the increased Hb F production in adults with hereditary persistence of fetal hemoglobin or delta beta-thalassemia is directed mainly by gamma-globin genes in cis to the deletion(s) responsible for these conditions. Here we review data on heterozygotes 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 the deletion of a single gamma gene does not affect the expression of the beta gene in cis but leads to a faster gamma-->beta switch postnatally.