IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 415 



by enzymatic digestion with tiypsin) is a troublesome problem and 

 present several difficulties. Liebold and Braunitzer (1959) have used 

 column chromatography, followed by paper ionopiioresis and/or paper 

 chromatography. Hill and Konigsberg (1960) have used countercurrent 

 distribution, followed by column chromatography and paper ionoj)horesis. 



The composition of the tiyptic peptides has been determined by 

 Braunitzer et al. (1960) and by Hill and Konigsberg (1960). The hemo- 

 globin chains were digested by means of proteolytic enzymes character- 

 ized with different specificities, like chymotrypsin or pepsin, so that 

 overlapping peptides were obtained; i.e., peptides containing either two 

 or more tryptic peptides or parts of two tryptic peptides and bridging 

 them together, so that their sequence could be determined (Braunitzer 

 et al., 1961; Hill and Konigsberg, 1961). The position along the peptide 

 chains of Hb-A of the peptides separated by fingerprinting is indicated 

 in Table I. 



By the conventional methods of the protein chemists, the partial 

 sequences obtained have been filled with all the amino acids in definite 

 order. Conclusive results have been published for the a chain of Hb-A 

 by Konigsberg et al. (1961), for the a and /? chain by Braunitzer et al. 

 (1961b), and for part of the /? chain by Goldstein et al. (1961). Many 

 years of work of several investigators are summarized in these few lines. 

 This work should be fully appreciated; it has required the constant 

 application of the ingenuity and skill of several experienced investigators 

 and has been concluded in a surprisingly short time. The two sequences 

 of the a chain, which have been independently determined, show complete 

 agreement. The amino acid sequences of the Hb-A peptide chains are 

 shown in Fig. 3. 



B. Hb-F 



The major component of hemoglobin prepared from fetal blood is 

 fetal hemoglobin, indicated as Hb-F. Hb-F usually accounts for 70-80% 

 of the total hemoglobin of a full-term infant (Jonxis, 1959) ; adult 

 hemoglobin appears in the red cells of fetuses at about the thirteenth 

 week of fetal life (Walker and Turnbull, 1955) and increases in relative 

 proportion until it completely replaces Hb-F by the end of the first year 

 of postnatal life. Hb-F is, however, observed in adults affected by 

 acquired or hereditary anemias, like thalassemia major or sickle-cell 

 anemia. High levels of Hb-F have also been found in some healthy 

 Negro adults (Edington and Lehmann, 1955) ; this condition has been 

 designated "hereditary persistence of Hb-F" (Jacob and Raper, 1958). 



Hb-F is characterized by an electrophoretic mobility only slightly 

 different from that of Hb-A. Hb-F is usually characterized and meas- 



