438 CORRADO BAC.LIONI 



critical marriages involving individuals with two of these hemoglobins 

 can be encountered. 



Allelism for most of the abnormal hemojilobin genes has been 

 postulated because of the absence of Hb-A in individuals having two 

 abnormal hemoglobins. Individuals ha\ing Hb-S and Hb-I),.unjab or 

 having Hb-8 and Hb-N do not show any Hb-A, even in trace amounts. 

 The first exception to the observation that persons with two abnormal 

 hemoglobins do not have any Hb-A was rej)orted by Smith and Torbert 

 (19581. These authors described the occurrence in a family of Hb-!S 

 and of a second abnoniial hemoglobin (Hb-Hopkins-2) ; in all the 

 members of this family showing both abnormal hemoglobins, Hb-A also 

 was found to be present. Smith and Torbert (1958) reported a three- 

 generation pedigree showing evidence for independent segregation of the 

 two abnormal hemoglobin genes. 



Atwater et al. (1960a) have reported the presence in two sisters of 

 four hemoglobins; in the three children of the two sisters, presumably 

 married to normal individuals, either no abnormal hemoglobins or only 

 one abnormal hemoglobin w-as observed (Fig. 8). Other individuals with 

 three (Cabannes and Portier, 1959) and four hemoglobins (Raper et a/., 

 1960) have been reported. The existence of two hemoglobin genes is 

 shown by the segregation of the abnormal hemoglobins in the families 

 reported by Smith and Torbert (1958) and Atwater et al. (1960a). 

 Atwater et al. (1960a) suggested possible schemes of inheritance of these 

 genes; they considered it most likely that these genes are located on two 

 different chromosomes. The possibility that the two genes are located far 

 apart on the same chromosome should also be considered ; the small num- 

 ber of individuals observed does not provide definite information on the 

 position of the tw^o genes. 



C. GENETIC AND BIOCHEMICAL RELATIONSHIPS 



Of particular interest is the presence in two members of the family 

 reported by Atwater et al. (1960a) of four electrophoretically distinct 

 hemoglobins. Baglioni and Ingram (1961) have investigated the chemi- 

 cal alterations of these four hemoglobins, which have been called Hb-A, 

 Hb-G, Hb-C, and Hb-X, according to the order of migration in electro- 

 phoresis. The Hb-C from this family was found to be identical to the 

 Hb-C described by Hunt and Ingram (1960) and consequently altered in 

 the /? chain. The Hb-G (designated Hb-Gphuadeiphia) was found to be al- 

 tered in the a chain, where a lysine substitutes for an asparagine residue. 

 Hb-X was found to contain the abnormal peptides characteristic of both 

 Hb-C and Hb-Gpi.jiadeiphia; Hb-X is thus abnormal in both its a and ft 

 peptide chains. A similar situation has been described by Itano and 

 Robinson (1960) for the individuals of the family reported by Smith 



