450 CORRADO BAGLIONI 



sickle-cell, tlialasscmia. Since the amount of any ahnoiinal licniof^lobin 

 is found to be lower than that of llh-A in heterozyjrotes for an abnormal 

 hemoglobin gene, the inversion of the Hb-A abnormal iiemoglobin ratio 

 has been thought to be characteristic of thalassemia in combination with 

 an abnormal hemoglobin gene. This type of thalassemia has been defined 

 "interacting" thalasst'mia and combinations of this tyjie of thalassemia 

 with Hb-C, Hb-D, and 111)-!^ have also been described (({uoted in Leh- 

 mann, 1960). These lu'moglol)ins have been shown to have altered {3 

 chains (Hb-D is presumably of the Hb-Dp„„jaij type). 



Thalassemic individuals in whom the ratio Hb-A/abnormal hemo- 

 globin is not invei-ted have been reported for the Hb-S/thalassemia 

 combination and for the Hb-C/thalassemia combination (Zuelzer et al., 

 1956; Zuelzer and Kaplan, 1954). The thalassemia in these individuals 

 is thus of a "non-interacting" tyjie. Examination of some of these indi- 

 viduals has shown that the non-interacting thalassemia is of the non- 

 increased Hb-As type. Interaction of the non-increased Hb-Ao type 

 thalassemia with Hb-I, resulting in an inversion of the Hb-A/Hb-I ratio 

 has been reported by Atwatcr et al. (1960b). Hb-I is known to be altered 

 in the a chain (Murayama and Ingram, 1959). Thalassemic genes may 

 thus interact with a or p mutant genes and be of the non-increased or 

 increased Hb-Ao type, respectively. 



2. Formal Genetics of Thalassemia 



Several marriages of persons affected by Hb-S/thalassemia or Hb-C/ 

 thalassemia combinations have been reported in the literature. (For a 

 review, see Rucknagel and Neel, 1961.) In most marriages only children 

 either heterozygous for thalassemia or heterozygous for the abnormal 

 S or C hemoglobins are born. The thalassemia in these families is of the 

 increased Hb-Aa interacting type. The thalassemic gene in these families 

 behaves as if allelic to the /3^ or y8*^ genes. However, in some similar 

 marriages, normal children, or children with thalassemia or sickle-cell 

 trait or with sickle-cell/thalassemia, are born (quoted in Ingram and 

 Stretton, 1959b). These findings indicate non-allelism of the thalassemic 

 gene concerned with the fi^ or /3^ genes. The thalassemia in these families 

 is usually of the non-increased Hb-Ao, non-interacting type. 



In the marriage of the Hb-I thalassemic individual reported by 

 Atwater et al. (1960b), only children with the thalassemic trait were 

 i)orn. It may be pointed out that this thalassemic gene is of the non- 

 increased Hb-Aa type and was shown to interact with the «' gene; it is 

 not proved, because of the very small number of individuals in this 

 family, whether this thalassemic gene behaves as if allelic to the «' gene, 

 as the family data suggest. 



