The occurrence of the alpha G-Philadelphia-globin allele on a double-locus chromosome.

Abstract Hb G-Philadelphia, an alpha-globin allele, is expressed as either 20%, 30%, or 40% of the total hemoglobin. Restriction analyses published thus far have shown that among persons with 30% and 40% hemoglobin (Hb) G the alpha G allele is seen only in a single-locus haplotype. We now report the identification of a second haplotype in which the alpha G allele is found in tandem with an alpha A allele. This haplotype has been found present in DNA from the members of one family in which Hb G is expressed as 20% of the total hemoglobin, determined by both cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC). Synthesis was balanced in all individuals. The identification of a variant alpha-globin allele in two distinct haplotypes presents the possibility of independent mutation. However, an alternative explanation cannot be ruled out; namely, that the original allele may have become distributed among the two haplotypes by unequal crossing-over.