Gamma‐chain heterogeneity of fetal hemoglobin in nonblack β‐ and δβ‐thalassemia and hpfh heterozygotes and homozygotes

The fetal hemoblobin (Hb F) of a few hundred nonblack patients with a heterozygosity or homozygosity for β‐thalassemia (β‐thal), δβ‐thalassemia (δβ‐thal), and some forms of the hereditary persistence of Hb F (HPFH) was isolated by DEAE‐cellulose chromatography and further characterized by high‐pressure liquid chromatography. Quantitative data for the three types of γ chain ( A γ T , A γ I , and G ‐γ) were compared with those obtained for the Hb F from black patients with similar conditions. The G γ chain levels in nonblack β‐thal heterozygotes varied greatly and did not fall into two distinct groups with high or low levels, as has been observed in blacks. The level of the A γ T chain in A γ T heterozygotes did not differ significantly when this anomaly was in cis or in trans to the β‐thal determinant. Beta‐thalassemia homozygotes from Turkey and Yugoslavia, had G γ values varying between 40% and 80%. Only 13 of 34 patients carried the A γ T gene. Nine were A γ T heterozygotes with an A γ T /total A γ level averaging 39% and four were A γ T homozygotes. The G γ chain levels in nonblack δβ‐thal heterozygotes varied between 28% and 46%. An additional A γ T chain heterozygosity in cis to the δβ‐thal determinant demonstrated that over 90% of the γ chains is produced by genes in cis to this anomaly. Analyses of members of two relatively large families with β‐thal, δβ‐thal, and the A γ T chain heterozygosities and homozygosities occurring in different combinations allowed a more or less quantitative evaluation of the production of γ‐chain genes in cis or in trans to either of the two types of thalassemia determinants. Such calculations were possible both in simple heterozygotes and in persons with the β‐δβ‐thalassemia condition.