Abnormal arrangements in the alpha- and gamma-globin gene clusters in a relatively large group of Japanese newborns.

Data were obtained on blood samples from a relatively large group (264) of healthy Japanese newborns, collected at hospitals in Tokyo, Kurashiki, and Ube. The studies included an evaluation of anomalies in alpha-globin gene and gamma-globin gene arrangements using gene mapping and gamma-chain composition analyses. The results confirmed the rarity of alpha-thalassemia among Japanese; only a few babies had alpha-thalassemia-2 trait (the -3.7-kilobase [kb] deletion), while others had alpha-globin gene triplications (both the alpha alpha alpha anti-3.7 and the alpha alpha alpha anti-4.2 types). Among the gamma-globin gene anomalies that were observed, a few babies had the -A gamma-A gamma- globin gene arrangement or the -G gamma A gamma- type of deletion. The gamma-chain triplication (-G gamma-A gamma G gamma-A gamma-) occurred in 10 out of 256 newborns, and its frequency exceeded that of its corresponding -G gamma A gamma- deletion by a factor of 5. The restriction endonuclease XmnI was a useful tool, in addition to the enzymes Bg1II and BclI, to evaluate and confirm the gamma-globin gene deletion and triplication. The A gamma T variant, which is the product of a mutant A gamma-globin gene, occurred at a frequency of 0.156. The chromosome carrying this mutant A gamma gene had a characteristic haplotype that was originally seen in black and Mediterranean patients with Hemoglobin (Hb) S or with beta-thalassemia.