The Human Alpha-Globin Gene. The Protein Products of the Duplicated Genes Are Identical

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Abstract
To determine whether any heterogeneity exists in the human .alpha.-globin chain, i.e., whether the products of the duplicated genes are identical, the total sequences of 14.alpha.-globin chains were determined. Globin chains studied included 7 chains that were abnormal, 6 which were normal chains from the same individuals, and 1 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 3 others using the differing physicochemical properties of the mutant Hb. In the special situation of a double heterozygosity for an .alpha.-chain abnormality, the products of the 2 mutated genes were separated from each other and from the mixture of the products of the 2 normal genes. They were then investigated independently as this approach increased the precision of the work. 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 losses may occur when using ion-exchange procedures to purify small peptides. The absence of any heterogeneity at the level of the gene products of duplicated .alpha. loci was shown. The human .alpha.-globin chain should be considered homogeneous.