Studies of the proporation and synthesis of haemoblogin C Philadelphia in red cells of heterozygotes, a homozygote, and a heterozygote for both haemoglobin G and alpha thalassaemia.

The proportion of Hb G Philadelphia (alpha68-Asn leads to Lys) in heterozygotes has been found to have a well-defined bimodal distribution around means of 33% and 46% Hb G. microcytosis and hypochromia are consistently associated with the latter group, who also have a decreased ratio of alpha/beta-chain synthesis in the peripheral blood, but these characters are not linked to the Hb-Galpha gene, because a parent with microcytosis and 46% Hb Galpha may have offspring with 33% Hb G without significant microcytosis. In one family a subject with Hb G and Hb G2 but no Hb A or Hb A2 is presumably a homozygote for alphaG. This subject has microcytosis and a decreased ratio of alpha/beta chain synthesis. In another family a subject with Hbs H, G and G2 but without Hbs A or A2 is heterozygous for both Hb G and alpha thalassaemia I. These findings are compatible with the hypothesis that the alphaG mutation occurs on a chromosome with only a single alpha-chain locus and that the expression in heterozygotes as 46% or 33% Hb G is determined by the homologous chromosome in trans having either one or two normal alphaA genes respectively. The significance of this polymorphism for chromosomes carrying alpha-chain genes is discussed.