Is haemoglobin G alpha Philadelphia linked to alpha-thalassaemia?

ABSTRACT

The question, "Is Hb G alpha Philadelphia linked to alpha-thalassaemia?" was first posed because the abnormal haemoglobin is found in heterozygotes at a concentration greater than 25%, the proportion predicted from a 4 alpha-chain gene model. Globin chain biosynthesis was studied in a West Indian family in which one parent had beta + thalassaemia and the other was heterozygous for the G alpha Philadelphia chain gene. The former had a globin chain production ratio alpha/beta well above 1, while the latter had a ratio significantly less than 1. One child of the marriage had inherited the beta + thalassaemia from one parent and the G alpha Philadelphia chain gene from the other and showed the typical picture of alpha/beta-thalassaemia (alpha/beta ratio slightly above normal). It is explained in the discussion that the evidence favours a close linkage of 2 alpha-chain genes.