Chromosomes With One, Two, Three, and Four Fetal Globin Genes: Molecular and Hematologic Analysis

Analysis of DNA from 852 Island Melanesians has revealed a high frequency of single- and triple-7-globin genes in this population. Homozygotes for triple- and single-7 genes have normal hematologic findings, normal hemoglobin F (HbF) levels, and when there is coexisting athalassemia, appropriate levels of Bart's Hb (74) at birth. In addition, we have identified an individual with a quadruple-7 gene chromosome who also has a normal HbF level. All single-7 genes were A7, all triple-7 genes GγGγAγ.and the quadru- ple-7 gene GγGγGγGγ. Analysis of Gγ:Aγ 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 interchro-mo soreal recombination events.