Fetal hemoglobin (HbF) production varies over a 20-fold range and is under genetic control. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of HbF-containing F reticulocytes and F cells in patients with sickle ... Fetal hemoglobin (HbF) production varies over a 20-fold range and is under genetic control. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of HbF-containing F reticulocytes and F cells in patients with sickle cell anemia (SS; 603903) and nonanemic persons, Dover et al. (1992) observed that the F-cell levels were significantly higher in nonanemic females than males (3.8% vs 2.7%) and that F-cell production as determined by F reticulocyte levels in SS females was also higher than in SS males (17% vs 13%). Five factors have been hypothesized to influence the 20-fold variation in fetal hemoglobin levels in sickle-cell anemia: age, sex, alpha-globin gene number, beta-globin haplotype, and the X-linked F-cell production locus that regulates the production of HbF-containing erythrocytes (F cells). In studies of 112 SS patients living in France who were homozygous for the 3 common African beta-globin haplotypes (Benin, Bantu or Central African Republic, and Senegal), Chang et al. (1997) found that (1) FCP accounts for about 40% of the overall variation in HbF levels; (2) when the FCP influence is removed, beta-globin haplotype on chromosome 11p15 is associated with 14% of the remaining HbF variation; and (3) the other factors have little influence.