DISSECTING THE LOCI CONTROLLING FETAL HEMOGLOBIN PRODUCTION ON CHROMOSOMES 11P AND 6Q BY THE REGRESSIVE APPROACH

The changes in the type of haemoglobin (Hb) produced during embryonic, fetal and adult life, have served as a paradigm for understanding the developmental regulation of human genes. A genetically determined per sistence of fetal Hb synthesis has an ameliorating effect on beta thal assaemia and sickle cell anaemia, globally the commonest single gene d isorders. The search for the putative gene(s) controlling the level of fetal Hb production has been extremely difficult because this trait m ay be influenced by several factors. We have studied a large kindred w ith hereditary persistence of fetal haemoglobin (HPFH). Using a geneti c mapping strategy and statistical methods that account simultaneously for the effects of several genetic factors, we have demonstrated that in addition to the two factors (beta thalassaemia and Xmn I-(G) gamma site) on chromosome 11p, there is a third major genetic determinant f or fetal Hb production localized on chromosome 6q.