IX. GENETICS AND HUMAN HEMOGLOBIN CHEMISTRY 449 



sequence of these peptide chains is extremely similar (Ingram and Stret- 

 ton, 1961). These circumstances may increase the probability of unecjual 

 crossing-over involving the (3 and S loci. 



G. THE PROBLEM OF THALASSEMIA 



Thalassemia is a hereditary anemia which occurs connnonly in Medi- 

 terranean countries. Two main forms of the disease are recognized: 

 thalassemia minor, which occurs in individuals heterozygous for a thal- 

 assemic gene, and thalassemia major or Cooley's anemia, in homozygotes 

 (Valentine and Neel, 1944). Thalassemia minor is a mild hypochromic 

 microcytic anemia which may be asymptomatic, while thalassemia major 

 is a marked hypochromic anemia, characterized by anisocytosis and 

 accompanied by profound alterations of skull and bones, due to bone 

 marrow hyperplasia. Children affected by thalassemia major usually do 

 not reach adulthood and early death in the absence of constant medical 

 care and repeated blood transfusions is the rule. Several aspects of the 

 thalassemic diseases have recently l)een reviewed by Lehmann (1960) 

 and by Rucknagel and Neel (1961). 



1. Hemoglobins in Thalassemia 



In thalassemia major Hb-F is constantly present in amounts which, 

 together with the hematological picture, are characteristic of this dis- 

 ease. As much as 97% of the total hemoglobin has been reported to be 

 Hb-F in a thalassemic patient (Rich, 1952). This Hb-F appears to be 

 identical to Hb-F isolated from cord blood when analyzed by finger- 

 printing (Baglioni, unpublished). In thalassemia minor the ]iroportion 

 of Hb-F is very close to normal values. 



Kunkel and Wallenius (1955), and subsequently Ceppellini (1956) 

 and several others, have reported an increase of Hb-A. to values approxi- 

 mately double the normal values in individuals affected by thalassemia 

 minor. The Hb-Ao obtained from thalassemic patients has been found 

 to be indistinguishable from Hb-Ao from normal subjects by finger- 

 printing (Ingram and Stretton, 1961). Kunkel et al. (1957) and Carcassi 

 et al. (1957) found several exceptions to the rule of increased Hb-Aj 

 in thalassemia minor. This and other genetic observations have proved 

 the heterogeneity at the molecular level of thalassemia. 



Several combinations of a thalassemic gene with abnormal hemoglobin 

 genes have been reported in the literature (see Lehmann, 1960). Affected 

 individuals in general show a moderately severe microcytic anemia; the 

 range of variability is, however, quite wide. Sickle-cell/thalassemia is the 

 combination which is more frequently observed (Silvestroni and Bianco, 

 1952). Hb-S, Hb-F, and veiy small amounts of Hb-A may be present in 



