Genetics of Hb F/F cell variance in adults and heterocellular hereditary persistence of fetal hemoglobin

Hb F and F cell values in normal adults vary considerably with a continuous distribution that is substantially skewed to the right implicating a polyg enic influence. The high values of Hb F and F cells are transmitted in the condition referred to as heterocellular hereditary persistence fetal hemogl obin which should be regarded as a multifactorial quantitative trait, quite distinct from the classical pancellular hereditary persistence of fetal he moglobins. Several factors have been shown to influence F cell/Hb F levels in normal adults including age, gender, genetic determinants linked and unl inked to the beta-globin locus on chromosome 11p. Two trans-acting quantita tive trait loci for F cell variance have been mapped, one on 6q and the oth er on Xp, with at least one other implicated. As an initial step towards hu nting for the other quantitative trait loci we have carried out a prelimina ry analysis of F cell variance in 182 pairs of monozygotic and 373 pairs of dizygotic twins. The correlation coefficient of F cell variance in monozyg otic twins was 0.89, while that in the dizygotic twins was 0.51. Overwhelmi ng evidence for a strong genetic component in the control of Hb F/F cell le vels is provided by a heritability of 0.87. However, the role and extent of contribution from the quantitative trait loci on 6q and Xp are still not k nown.