Chromosomes with one, two, three, and four fetal globin genes: Molecular and hematologic analysis

Abstract

Analysis of DNA from 852 Island Melanesians has revealed a high frequency of single- and triple-γ-globin genes in this population. Homozygotes for triple- and single-γ genes have normal hematologic findings, normal hemoglobin F (HbF) levels, and when there is coexisting α thalassemia, appropriate levels of Bart's Hb (γ4) at birth. In addition, we have identified an individual with a quadruple-γ gene chromosome who also has a normal HbF level. All single-γ genes were (A)γ, all triple-γ genes (G)γ(G)γ(A)γ, and the quadruple-γ gene (G)γ(G)γ(G)γ(A)γ. Analysis of (G)γ:(A)γ ratios in cord bloods and HbF levels in adults showed that these additional γ genes are expressed and are down regulated appropriately by the fetal to adult Hb switch. Analysis of the restriction enzyme haplotypes of these various chromosomes indicates that intrachromosomal cross-overs are more likely to have produced these variants than interchromosomal recombination events.