426 CORRADO BACLIONI 



TIk' known allflisiu of the Ilh-S ;iii(l lll)-(" «;ciic> I l{aniicy, 1954) 

 was thus coiiliiiiicd at a strictly molecular lc\-('l. 'riicsc results estab- 

 lished a correlation between the abnoi-nial hemoglobins genes and the 

 linear structure of the peptide chains, the synthesis of which is con- 

 trolled by these genes. 



Several other abnormal liemoglobins were analyzed in a similar way 

 by Ingram and by others (see Table II). From the chemical studies of 

 the peptide chains of Hb-A (Ingram, 19r)9a), it is known which pej)- 

 tides in the fingerjirinting of this hemoglol)in belong to the « chain and 

 which belong to the (i chain (see Table 1 1. By fingerprinting the abnor- 

 mal hemoglobins it was possible to deteiinine the i)ej)ti(le chain altered 

 in these hemoglobins; i.e., peptides altered in fingerpiints of Hb-S, Hb-E, 

 and Hb-Upunjab were found to belong to the /? chain, pe|)tides altered 

 in Hb-I, Hb-Norfolk, and Hb-Gi-Miiad^ipina were found to belong to the a 

 chain. The alterations of the Hb-A variants have been assigned to one 

 or the other of the Hb-A peptide chains by this method of analysis oi' 

 by recombination experiments (Itano and Robinson, 1959; see Section 

 IV,D). The chemical formula of an abnormal hemoglobin can be written 

 by indicating with the hemoglobin designation the peptide cliain that 

 is altered, i.e., Hb-S = a-^ p.^, Hb-C = a-^ po"", Hb-I = as'iSa^. 



Ingram ( 1959a) suggested a one gene-one peptide chain relationship 

 for the Hb-A peptide chains. In this view each gene controls the syn- 

 thesis of one type of peptide chain. The structural genes determining 

 the amino acid sequence of the peptide chains arc designated with the 

 same symbols used to indicate the corresponding ])eptide chains; namely 

 the gene a^ carries the information for the synthesis of a^ chains and 

 the gene /3-^ for the sjmthesis of /?-^ chains. We can subdivide the Hb-A 

 variants into two categories: the a chain and the /? chain variants. The 

 Hb-S gene is defined as p^, the Hb-I gene as a', and so on. 



One of the most significant results of the chemical analysis of 

 abnormal hemoglobins is the discovery by Benzer et al. (1958) of the 

 heterogeneity of hemoglobins, which are indistinguishable by means of 

 physical methods of analysis. Three samples of Hb-D obtained from 

 individuals living in different countries were analyzed and found to 

 cany different peptide changes. These three Hb-D's are thus distinct 

 proteins and, more important, they are certainly produced by three 

 difTerent mutant genes. The importance of such observation should be 

 fully evaluated: the validity of genetic, ethnological, or anthropological 

 correlations established in the absence of a biochemical analysis at the 

 ultimate molecular level is in fact shown to be questionable. The 

 heterogeneity of licmoglobins having identical electi-ojihoretic and 

 chromatographic characteristics has also been demonsti'ated for Hb-0 



