Beta-globin-like gene cluster haplotypes in hemoglobinopathies.

Abstract

The pioneering work of Kan and Dozy () revealed by restriction endonuclease mapping a genetic variation in an HpaI recognition site about 5000 nucleotides from the 3′ end of the β-globin gene. Instead of a normal 7.6-kb fragment containing the β-globin gene, 7.0- and 13.0-kb variants were detected and were found in African Americans, Asians, and Caucasians. The 13.0-kb variant (HpaI+) was frequently associated with the sickle hemoglobin (Hb) mutation. Kan and Dozy () predicted that polymorphisms in a restriction enzyme site could be considered a new class of genetic marker and may offer a new approach to linkage analysis and anthropological studies. Based on limited data (), they reported that linkage to the wild-type HpaI-positive site was characteristic of West Africans while an HpaI-negative site typified East Africans. This finding did not show definitively that the mutation had occurred in two different chromosomal backgrounds, because a secondary mutation at the HpaI site could have postdated the sickle mutation.