A Search for Anomalies in the ζ,α,β, and γ Globin Gene Arrangements in Normal Black, Italian, Turkish, and Spanish Newborns

Abstract

Globin gene mapping analyses of DNA from numerous Black babies, and from newborns from Sardinia, Sicily, Turkey, and Spain have identified the following

A high incidence of α-thalassemia-2 heterozygotes among Black babies with less than 1% Hb Bart's at birth and a high incidence of α-thalassemia-2 among Sardinians, but not among Sicilian, Turkish, and Spanish babies. A relatively high incidence of ζ-thalassemia was present among Black babies only, while triplicated ζ was seen in four of the five populations. Two Black babies were each found to have a different θl deletion; two Sardinian babies had a newly discovered β 2.5 kb deletion between ζ and ψζ; four babies had the rare Bgl II polymorphism between ψζ and ψα; and one Black baby lacked the Eco RI site 3’ to ζ Quantitation of the ζ chain by reversed phase high performance liquid chromatography showed that two-thirds of the babies with four α genes (αα/αα) had levels between 0.1 and 1.0%, while nearly 90% of the babies with -α/αα had similar levels (averaging 0.2% for αα/αα 0.35% for -α/αα 0.75% for -α/-α). Additional data indicated that the occurrence and level of ζ are related to the level of β, i.e. the gestational age. The presence of a ζ triplication did not affect the level of ζ in cord blood. The extensive search for γ-globin gene anomalies resulted in the discovery of a chromosome with five γ genes, γ-Thalassemia was rare in all populations, while the -^Gγ-^Gγ- gene arrangement was mainly observed among Black babies; this arrangement is primarily responsible for high ^Gγ levels in cord blood samples. The strong correlation between the presence or absence of a C→T mutation at position -158 (measured in Xmn I digests) and the level of ^Gγ was confirmed for adult blood samples. A search for possible anomalies in the -δ-β- region through gene mapping with Eco RV gave negative results except for the discovery of a polymorphic site 5’ to δ in one of the 371 Black babies tested.