THE GAMMA CHAIN HETEROGENEITY OF FETAL HEMOGLOBIN IN BLACK BETA-THALASSEMIA AND HPFH HETEROZYGOTES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 58  (1) , 62-70
Abstract
High pressure liquid chromatography (HPLC) was applied to the HbF isolated from blood of numerous black patients with .beta.-thalassemia [thal] trait or homozygosity, G.gamma.-.delta..beta.-thalassemia trait, G.gamma.A.gamma.-HPFH [HbS-high HbF persistence] heterozygosity or the G.gamma.-[.delta.+.beta.+]-HPFH condition. The method allowed an accurate evaluation of the relative quantities of three of .gamma.-chain (G.gamma.,A.gamma.I and A.gamma.T) in the fetal Hb. The incidence of the A.gamma.T-chain in .beta.-thal heterozygotes and G.gamma.A.gamma.-HPFH heterozygotes is about the same as that observed in newborn blacks; about 1 of 5 blacks are heterozygous for this A.gamma.-chain variant. The A.gamma.T-chain was not detected in the 9 G.gamma.-.delta..beta.-thal heterozygotes or in the 8 G.gamma.-[.delta.+.beta.+]-HPFH heterozygotes. In most cases, the A.gamma.T-chain produced by the A.gamma. gene in trans to the .beta.-thal or HPFH determinant. The contribution by the .gamma.-chain genes in trans to the .beta.-thal or HPFH determinant is about 15% of the total .gamma.-chain production in both conditions. Three black .beta.-thal heterozygotes (and 5 additional relatives) had the A.gamma.T gene in cis to the .beta.-thal determinant. Four of these patients had a low level of G.gamma.-chain (the adult level) and the contribution by the A.gamma. gene in cis to the .beta.-thal determinant was about 3 times that of the A.gamma. gene in trans. The 4 additional patients, all members of 1 family, had a high level of G.gamma.-chain (the newborn level) and the contribution of the A.gamma. gene in cis was 1/2 of that seen in the previously mentioned 4 patients and that of the A.gamma. gene in trans was essentially the same. The genetic anomaly causing high G.gamma. levels in adult .beta.-thal heterozygotes is evidently linked to the .beta.-thal determinant and 1 of its primary effects is a decreased synthetic expression of the A.gamma. gene in cis to the .beta.-thal determinant.