The human alpha-globin gene. The protein products of the duplicated genes are identical.

In order to determine whether any heterogeneity exists in the human alpha-globin chain, i.e. whether the products of the duplicated genes are identical, we have determined the total sequence of 14 alpha-globin chains: seven of these were abnormal, while six were normal chains from the same individuals, with one additional sample which consisted of the alpha chains from a normal control. In the individuals heterozygous for an alpha-chain abnormality, the product of a single alpha-gene could be isolated from that of the three others using the differing physicochemical properties of the mutant haemoglobins. In the special situation of a double heterozygosity for an alpha-chain abnormality, the products of the two mutated genes were separated from each other and from the mixture of the products of the two normal genes. They were then investigated independently, this approach increased the precision of our work. During the course of the present investigation, sequence determinations were mainly performed on large fragments of the chains, which were purified exclusively by gel chromatography. In this way mixtures of products of several genes could be studied, thereby overcoming the risk of losing peptides differing slightly in sequence. Such loss may often occur when using ion-exchange procedures to purify small peptides. Our results show the absence of any heterogeneity at the level of the gene products of the duplicated alpha loci. Thus the human alpha-globin chain has to be considered as homogeneous.