γ-Globin gene triplication and quadruplication in Japanese newborns Evidence for a decreased in vivo expression of the 3'-Aγ-globin gene

AbstractCord blood samples of 113 Japanese babies from Kurashiki, Japan, were analyzed for the presence of possible modifications in γ-globin gene arrangements and for changes in the relative quantities of the γ chains Gγ, Aγ, and its variant AγT. As many as 9 babies had the γ-globin gene triplication, one a γ-globin gene quadruplication, and two a γ-globin gene deletion. The triplication and quadruplication involved cross-overs within the Gγ- and Aγ-globin genes resulting in a hybrid gene with the 5'-segment being derived from the Aγ and the 3'-segment from the Gγ-globin gene (-AGγ-). The Gγ value of the 9 babies with the -Gγ-AGγ-Aγ-globin gene arrangement averaged 8̃0% and that of the baby with -Gγ-AGγ-AGγ-Aγ- was 78%. Four of the 9 babies with the triplication and the baby with the quadruplication had an AγT mutation in trans; in these babies, the Aγ chain level (from the Aγ-globin gene in 3'-position in the tri- and quadruplication arrangements) was decreased to about one-third and one-sixth of the level observed in the simple AγT heterozygote. This observation supports the suggestion that transcription beginning at the 5'-γ-globin gene interferes with that of the 3'-γ-globin gene