444 CORRADO HACLIOXI 



a'^/«^ lu'tt'i'Dzyiioiis l);il)i('s and the (rniicc> coiiiMiic rainlonilN' with fj/'' oi' 

 y/ (liinci's in a way apparently siniilai- to that sn^^t'.stt'd to cxphain the 

 pivscncc of I'oui- h('iiioii;lul)int5 in individuals doubly ht'tcrozygous fof an 

 a' and a /3 chain ahnonnality (Fig. 10). 



F. lib- A:; VARIANTS 



1. 8 (linin ]'ariants 



Ccppellini (1959a) discovered an abnoinial minor component, called 

 Hb-Bj, which migrated in electrophoresis more slowly than Hb-Ao. 

 Ccppellini < 1959b) suggested that Hb-Ba is related to Hb-Aa since the 

 amount of Hb-Ao in the Hb-Ba carriers is decreased to half its normal 

 N'alue and the sum of these two fractions equals the normal value of 

 Hb-Aa. ^Moreover, in thalassemia heterozygotcs the amotmt of both 

 Hb-A, and Hb-B, is doubled (Ccppellini, 1959b). 



Huisman and Meyering (1960) have also describt'd a minor com- 

 ponent with an electrophoretic mobility similar to that of Hb-Bj. Horton 

 et al. (1961) have reported an individual apparently homozygous for the 

 Hb-Bo gene; the chemical study of Hl)-B:. has shown that only one pep- 

 tide is different in the fingerprint of this hemoglobin, when conijiared to 

 the fingerprint of Hb-Ao. 



The peptide chains of Hb-An and of Hb-B.. have been separat(Yl and 

 fingerprinted by Horton et al. (1961), and the altered peptide was shown 

 to belong to the 8 cliain. The amino acid substitution may presumably 

 involve a glycine in position 16 of the 8^- chain, which may be substi- 

 tuted by an arginine residue in the S"- peptide chain (A. 0. W. Stretton, 

 personal communication) ; this suggestion is in accord with the chemical 

 findings of Horton et al. (1961). These facts prove the existence of the 

 8 gene as an independent genetic entity. 



2. Formal Genetics of the 8 Chain Variants 



Ccppellini (1959b) reported a double heterozygous ))ropositus /3-^ 8''-/ 

 ^s gAo i-n-ii-i-iefj ^Q .J noniial woman. Their six children were found to be 

 either Hb-S or Hl)-B2 carriers; the alternative segregation of the j3^ 

 and 8"- genes suggests linkage of the ^ and 8 loci, the 13^ and 8"- genes 

 i)eing in repulsion in the propositus (see Fig. 11). 



Huisman et al. (1961) have reported a family in which scn-eral mem- 

 bers exhibit Hb-Bo plus thalassemia minor of the "high-A." type (see 

 Section IV,G). This type of thahissemia behaves as if allelic to the (3 

 locus (see Ingram and Stretton, 1959b) and the abnormal gene may be 

 indicated as [3"^^ gene. The /3'^^' and 8^- genes do not segregate in the 

 family report(>d by Huisman et al. (1961), suggesting linkage of these 



