Five haplotypes in Black β-thalassaemia heterozygotes: three are associated with high and two with lowGγ values in fetal haemoglobin

Abstract

Genotypes at 7 different polymorphic restriction sites (5'' to the .epsilon. gene, at the G.gamma., at the A.gamma., at the .psi..beta., 3'' the .psi..beta., at the .beta., and 3'' to the .beta. genes) were analyzed by restriction endonuclease mapping of the DNA from 66 Black .beta.-thalassemia heterozygotes from Georgia and several of their normal relatives. Five different haplotypes were observed. Three of these were associated with high G.gamma. values in the small amount of Hb F (0.8-8.3%) present in the blood of these patients and 2 with low G.gamma. values. One haplotype [- + - + + + +] that occurred on 2 of every 3 .beta. thalassemia chromosomes was associated with high G.gamma. levels, and is the same as that found in some Black SS patients also having high G.gamma. values. Two others [- + + - + - +] and [- + - - + + +] were also associated with high G.gamma., while 2 [- - - - + + +] and [+ - - - - + +] were associated with low G.gamma.. Variation in hematological data, mainly MCV [mean carpuscular volume] and MCH [mean carpuscular Hb] values, was found to be caused in part by the type of .beta.-thalassemia (defined by its haplotype) and by the presence of an additional .alpha.-thalassemia-2 heterozygosity or homozygosity.