The chemical and genetic relationships between hemoglobins S and G-San Jose.

I N AN EARLIER report,' Schwartz and co-workers presented evidence which suggested that the genes controlling the formation of hemoglobins S and GG an Jose are nonallelic. Recent studies2 have shown that these hemo-globins differ from hemoglobin A as follows: Each sequence represents the first eight amino acids from the amino terminus of the $-chains. In view of recent suggestions on the nomenclature of hemo-glcbin,' this G hemoglobin is designated aAA fl77 .1117 The results of these two studies are difficult to understand in view of recent evidence4 which indicates that the sequence of amino acids in the a-chains is controlled by a single gene. If this is correct, then allelic genes would be expected to control the structure of the a-chains of hemoglobins C and S. A solution to this problem has been obtained by re-analyzing the hemoglobins from individuals of the family originally studied by Schwartz et al.; this will be referred to in this paper as the hemoglobin G-S-thalassemia family. With the aid of chemical methods for comparing the structure of hemo-globins A, S and G, the sequences shown above represent the only differences found among these hemoglobins. Furthermore, the chemical methods confirmed the presence of the hemoglobins originally described in members of the G-S-thalassemia family, except for the propositus (111-1). The component which was identified previously in this individual as hemoglobin G is a mixture of hemoglobins which are present in increased amounts although normally present in minor amounts. Because the earlier genetic analysis was based primarily on the observation that this individual possessed hemoglobin G, the findings reported here make it unnecessary to assume that nonallelic genes control the structure of the $-chains of hemoglobins S and G. Although direct genetic evidence is lacking, it is probable that these genes are alleles. Hemolysates were prepared5 from toluene-extracted, washed erythrocytes. Paper electro-phonetic and chromatographic analyses of the tryptic peptides from various hemoglobins were performed as described earlier.2 Electrophoretic analyses of hemoglohins by the moving boundary method,1 on starch blocks5 or starch gels7 were performed as previously From the Laboratory for the Study of Hereditary and Metabolic Disorders and the De