IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 



465 



human hemoglobin genes and needs to be substantiated by more direct 

 and critical evidence. 



It cannot be excluded on genetic grounds that the high F condition 

 results from an inactivation or a deletion of the two linked genes (3 and 

 8, however unlikely a recurrent genetic event of this type may be; the 

 concomitant elevation of Hb-F still remains to be explained. It has been 



70 % S 





I I 

 I I 

 I I 



si 



0" 



S 



I ! 



30 %F 



(r/) / \r' -r: 



Fig. 14. Schematic representation of the postulateil genotype of incUvicluals 

 heterozygous for the "hereditary persistence of Hb-F" and for the f3^ gene. The 

 normal "operator" or "regulator" gene (Neel, 1961) is indicated as o*; the abnormal 

 allele responsible for the persistence of Hb-F is indicated as o~. The arrows illustrate 

 the dimers sjTithesized under the control of the hemoglobin genes and the hemo- 

 globins produced by random combination of the dimers (capital letters). The (i and 

 5 genes in <?(« with the o~ mutation are supposedly inactive (see Section V,C) ; it is 

 not known whether y chains are synthesized under the control of the y locus in cis 

 with the o~ mutation or whether both the y loci are active. The relative levels of 

 Hb-S and Hb-F observed in these individuals are also .shown. 



suggested (V. M. Ingram, unpublished) that the difference between 

 thalassemia and high F condition may reside in the production of a 

 defective RNA-template in the former and in no production at all of 

 RNA-templates in the latter, if the /3 and 8 genes have been deleted. If 

 messenger-RNA molecules compete for the ribosomal sites of protein 

 synthesis, in thalassemia the ribosomes would be occupied by the defec- 

 tive messengers, while in the high F condition the ribosomes may be free 

 to accept y chain RNA-templates. 



