Organization of a - Globin Genes in Hb Hasharon ( a 47 asp - his ) Carriers

T HE DISTRIBUTION of the percentage of a globin variant chains in humans is tnimodal, with maxima around 45%, 33%, and 25%’; the latter value is the most commonly found and comparison with the usual 45%-50% value for f3 globin mutants was the basis for the suggestion2 that a globin genes are duplicated in humans. Thus, the dyploid number of a genes would be 4, one of which should be the mutated one. Subsequent genetic studies of individuals carrying mutant a globin genes,36 of the inheritance pattern of South East Asian a, and a2-thalassemia,7 together with direct a globin gene number determination by eDNA-DNA hybridization studies in normal and a thalassemic subjects,8 5 confirmed this hypothesis and showed that gene duplication occurs in many different races. However, the possibility that a “normal” nonthalassem ic haploid chromosome complements with only one globin gene exists in at least some populations, is suggested by the finding of variant a chains occurring in the 33% and 45% range.”6”7 In these cases the mutation is believed to have occured on the single a gene that would be found in conjunction with either the “normal” set of duplicated genes (in the first case) or with the single gene set (second case). The one a globin gene/aploid chromosome set hypothesis could not be confirmed by eDNA-DNA hybnidization studies of individuals having the HbJ Mexico variant at levels of 30% and 40%’ ; globin RNA analysis’8 of carriers of HbJ Tonganiki (a mutant usually present at the 50% and 100% level in hetenozygotes and homozygotes, respectively) suggested the existence of an a thalassemic gene in conjunction with the mutant a globin. We have now studied by restriction enzymes of two unrelated Italian families with Hb (a 47 asp his)’9’2#{176} frequently occurring in the Polesine area in Italy,2”22 where it is usually observed at the 33% level. We show here that this variant is associated to an a globin gene deletion.