Gene regulation and deregulation: a beta globin perspective

The study of the beta globin gene has provided great insights into the mech anisms of gene regulation and expression. In this review, we consider the n ormal regulation and expression of the beta globin gene and illustrate how the various steps may be affected, providing a basis for understanding the molecular pathophysiology of beta thalassemia. Mutations causing beta thala ssemia can be classified as beta(degrees) or beta(+) according to whether t hey abolish or reduce the production of beta globin chains. The vast majori ty of beta thalassemia is caused by point mutations, mostly single base sub stitutions, within the gene or its immediate flanking sequences. Rarely, be ta thalassemia is caused by major deletions of the beta globin cluster. All these mutations behave as alleles of the beta locus but in several familie s the beta thalassemia phenotype segregates independently of the beta globi n complex, and are likely to be caused by mutations in trans-acting regulat ory factors. (C) 2000 Harcourt Publishers Ltd.