Association of the level of G_γ chain in the fetal hemoglobin of normal adults with specific haplotypes

Abstract

The levels of G_γ chain in the fetal hemoglobin of more than 40 Black and Caucasian females were determined with a sensitive high performance liquid chromatography procedure and were correlated with their haplotypes, defined by the presence or absence of 10 different restriction sites. Blood was collected during the 16th and 31st week of pregnancy because of a slightly elevated level of Hb F which facilitated the isolation of this protein from a relatively small sample. Four distinct G_γ levels were observed, each being associated with a specific haplotype. Homozygosity for sub-haplotype A [-+ +-+ +] is associated with high G_γ values (60-70%); that for sub-haplotype B [––-+] with low levels (25-30%); and that for sub-haplotype C [+––-] with very low levels (10-15%) (restriction sites listed are Hinc II at e; Xmn 1 5′ to G_γ; Hind III at G_γ and A_γ; Hinc II at β and 3′ to it). Sub-haplotype D [(14)-+–+] with a rare polymorphism 5′ is associated with extremely high G_γ values. Hb F levels were low (< 2.5%) and were independent of the haplotype. It is speculated that, yet unknown, variations in the DNA of gene activity controlling regions are responsible for the differences in G_γ value.