Compensation of β Chain Synthesis by the Single β Chain Gene in Hb Lepore Trait

Abstract

ALTHOUGH many aspects concerning the synthesis of the α and β chains of haemoglobin are understood, others, notably the control mechanisms, need clarification. One important question is whether a single gene for α or β chains respectively can compensate for a deficiency of synthesis from its allele. For example, in β thalassaemia trait is there any compensatory synthesis of β chains from the normal gene? This can be answered by examining the relative rates of synthesis of the β chains in patients heterozygous for a Hb Lepore. This is a class of haemoglobin variants composed of α chains and fused δβ chains. The N-terminal sequence of the hybrid chain corresponds to that of the δ chain whilst the C-terminal sequence corresponds to that of the β chains. It is thought to have arisen during meiosis by a misplaced synapse of the δ and β loci followed by a non-homologous cross-over¹. Consequently, in the red cell precursors of heterozygotes there is only one normal β gene and one normal δ gene: their alleles are fused —δβ—.