462 CORRADO BAG LION I 



pensatory phenomenon when the syntliesis of Ilh-A is im]jaircd, as in 

 thalassemia major (Rich, 1952). 



Hb-F does not seem to be evenly distributed in the red cells of 

 anemic jKitients. Bradley et al. (1961) have reported that Hb-F and 

 ilb-S arc unevenly distributed in the red cells of sickle-cell anemic 

 patients. Similar results have been obtained by the Kleihauer et al. 

 (1957) method of analysis by Thompson et al. (1961) and by Witchener 

 et al. (1961). Identical observations have been reported for the distribu- 

 tion of Hb-F in red cells of subjects affected by thalassemia major 

 (Thompson et a/.. 1961). Two distinct cell populations are observed in 

 these patients by this method of analysis, one with high amounts of 

 Hb-F and the other with rather small amounts of Hb-F (Thompson 

 et al., 1961). The Hb-F in the red cells of severe anemic patients seem 

 thus to have a clonal distribution, with clones of red cells containing 

 Hb-F and clones of red cells apparently of the normal adult type. 



C. HEREDITARY PERSISTENCE OF Hb-F 



Edington and Lehniann (1955), and subsequently other investigators, 

 have reported a condition in which high proportions of Hb-F are found 

 in healthy Negro adults. This condition has been designated "hereditaiy 

 persistence of Hb-F" by Jacob and Raper (1958), since Mendelian 

 inheritance of this anomaly was shown by family studies. The gene 

 responsible for the persistence of Hb-F during adult life has also been 

 called "high F" gene. In carriers of this gene 20 to 30% of the hemo- 

 globin is Hb-F; approximately the same amount of Hb-F is observed 

 in individuals heterozygous for the high F gene and for the abnormal 

 hemoglobin genes yS^ or fi^. It is quite remarkable that no Hb-A is 

 present in these heterozygous individuals (Jacob and Raper, 1958; Went 

 and Maclver, 1958). 



Several marriages of heterozygotes for the high F and jS^ or fS^' genes 

 with normal partners have been reported (Bradley et al., 1961 ; Thomp- 

 son et al., 1961; Kraus et al., 1961; Maclver et al., 1961) ; children born 

 from these marriages inherit either the high F gene or the abnormal 

 hemoglobin gene. 



The high F gene thus behaves as if allelic or closely linked to the /3 

 locus. It has been suggested that the high F abnormality is the result 

 of a mutation at the /3 locus and that the production of Hb-F is a com- 

 pensatory phenomenon (Bradley and Conley, 1960). The high F gene in 

 this view is interpreted as a thalassemic-like gene, suppressing com- 

 pletely the production of p peptide chains. However, the majority of the 

 heterozygotes for a thalassemic gene do not show any increase of the 

 Hb-F level over normal values. Individuals heterozygous for the high 



