Fetal hemoglobin variants identified in adults through restriction endonuclease gene mapping methodology

Abstract

It has been found possible to detect the presence of some gamma chain abnormal fetal hemoglobins in adults through analysis of genomic DNA with selected restriction endonucleases. These variants are Hb F-Hull (A gamma 121Glu----Lys) which was observed in eight adult members of five families, Hb F-Pendergrass (A gamma 36Pro----Arg) in five adult members of one family, and Hb F-Port Royal (G gamma 125Glu----Ala) in 32 adult members of 17 families. The analyses were extended to include haplotyping, which involved 12 different restriction sites. The Hb F-Port Royal anomaly was only present on a chromosome with two G gamma genes (the 5'-G gamma-G gamma-3' globin gene arrangement) which may have arisen through gene conversion or point mutations. It appears likely that the mutation resulting in the 125Glu----Ala substitution occurred once on a 5'-G gamma-G gamma-3' chromosome, while additional base substitutions, gene conversions, and/or cross-over events are responsible for the association of the F-Port Royal anomaly with different chromosomes, as characterized by different haplotypes.