γ‐Globin gene triplication and quadruplication in Japanese newborns

Cord 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.