Genetic Control of Hemoglobin Synthesis

Abstract

There is compelling evidence that human hemoglobin is determined in part by a complex genetic locus which involves duplication. An hypothesis is presented concerning the control of hemoglobin synthesis, based on known properties of regions of genetic duplication. Many abnormalities such as the variants of thalassemia, the high-fetal-hemoglobin and high -A2-hemoglobin syndromes, and hemoglobins H and Bart''s may result from combinations of the abnormal alleles which can result from unequal but homologous crossing over at the hemoglobin locus. One clear example of this phenomenon has already been described, the Lepore trait, where the resulting fusion gene determines a physiologically active hemoglobin variant. The significance of the model developed in providing a mechanism for the maintenance of genetic polymorphisms is stressed, and its possible relevance to cellular differentiation and other important problems in human genetics discussed.