IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 



445 



two genes in coui)ling. It must be pointed out that in double lu'terozygotes 

 for thalassemia and the 8^- gene, the increase of Hb-A^ level is identical, 

 whether the two mutant genes are in coupling /3'^^^ 8^-/y8'^ S'^- (Huisman 

 et al, 1961) or in repulsion /J^h 8VyS' S''^ (Ceppellini, 1959a). 



Not enough genetic data have been accumulated to determine the 

 extent of the linkage between the (i and the 8 loci. It seems unlikely, 

 moreover, that enough data can be found to determine the fine genetic 

 structure of the ft and 8 loci. The /3 and 8 genes seem, however, to be 



Fig. 11. Schematic explanation of the presence of four hemoglobins in the 

 propositus of the family reported by Ceppellini (1959b). The genotype is illustrated 

 on the left; the (3 and 5 loci are shown in linkage as suggested by the alternative 

 segregation of the /js and 5^^ genes. The arrows show the different dimers syn- 

 thesized and their random combination to form the four hemoglobins indicated by 

 capital letters. 



under a common genetic control: (i) Hb-A and Hb-Ao appear in fetuses 

 at approximately the same age and increase in concentration in a parallel 

 way (Kunkel et al., 1957) ; {2) both Hb-A and Hb-Ao are absent from 

 individuals homozygous for the "hereditary persistence of Hb-F" 

 (Wheeler and Krevans, 1961) or for the Hb-Pylos gene (Fessas et al., 

 1962). These relationships in the behavior of the ft and 8 genes and 

 the family studies suggest a functional and topographical linkage of 

 these genes. 



3. The a Chains of Hb-A. 



Shooter et al. (1960) have shown in a person apparently homozygous 

 for the abnormal hemoglobin Gibadan the presence of a minor component 

 with an altered electrophoretic mobility, called Hb-Gi... Hb-Gn.adan bas 



