IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 447 



ically identical (Ingram and Stretton, 1959; Muller and Jonxis, 1960); 

 they are under the control of the same a gene. The So dimers, like the 

 y., dimers, combine in a random way with all the types of ao dimers 

 present in the last stage of Hb-Aa synthesis (Fig. 12). 



4. The Problem of Hb-Lepore 



Gerald and Diamond (1958) described a patient of Italian extrac- 

 tion affected by a severe anemia, clinically classified as thalassemia 

 major. The propositus, his mother, and four maternal relatives showed 

 an electrophoretically slow moving abnormal hemoglobin called Hb- 

 Lepore, from the name of the family, in concentration of approximately 

 10 to 15% ; they were found to be affected by microcytemic anemia. 

 The father of the propositus was found to be a ft'^^/p^ heterozygote and 

 the severe anemia in the propositus was thought to result from the 

 interaction of the jS"^*^ gene and of the Hb-Lepore gene. Similar cases of 

 an electrophoretically slow moving abnormal hemoglobin, associated with 

 microcytemic anemia have been reported among Italians (Silvestroni and 

 Bianco, 1958), Papuans (Neeb et al., 1961), and Greeks (Fessas et al., 

 1962). This condition seems to be relatively frequent among patients 

 with microcytemic anemia in Greece (Fessas et al., 1962). 



The abnormal hemoglobin, always present in concentration of about 

 10-15%, has been alternatively classified as Hb-G (Silvestroni and 

 Bianco, 1958), Hb-Pylos (Fessas et al, 1962), or Hb-Lepore (Neeb 

 et al., 1961). Individuals apparently homozygous for the Hb-Lepore 

 gene or for the Hb-Pylos gene have been reported ; they are characterized 

 by a complete absence of Hb-A and of Hb-Ao in the case described by 

 Fessas et al. (1962) and presumably in the two cases of Neeb et al. 

 (1961). In the heterozygotes the amount of Hb-As is reduced to about 

 half the normal value (Fessas et al.. 1962). 



Gerald et al. (1961) have briefly reported the results of their chemical 

 studies on Hb-Lepore and Hb-Pylos; these hemoglobins give fingerprints 

 indistinguishable from those of Hb-Ao. Moreover, some of the peptides 

 of Hb-Lepore were analyzed and found to have an amino acid composi- 

 tion identical to homologous peptides of Hb-Ao. Neeb et al. (1961) have 

 also fingerprinted Hb-Lepore from Papuans and have obtained a peptide 

 pattern indistinguishable from that of Hb-Ao. Hb-Lepore has presum- 

 ably normal a peptide chains, since no alteration of the fingerprint pat- 

 tern of the a chain has been observed, but mainly because normal Hb-F 

 is present in Hb-Lepore carriers; one would expect that if any abnormal 

 ao dimers were present, they would associate randomly with yz as well 

 as So dimers. The abnormality in the "S" chain of Hb-Lepore has not 

 been discovered, but it may possibly be hidden in the "core" of this 



