DNA polymorphism and molecular pathology of the human globin gene clusters

Abstract

In the past few years there has been intensive study of the human globin genes. This study has provided important insights into normal gene structure and function and the nature of molecular defects leading to a set of inherited diseases. In turn, this information forms the basis for rational design of specific tests for prenatal diagnosis of particular forms of beta-thalassemia. Several areas demand further investigation. First, we need to know more about the region within the beta-gene cluster in which recombination appears to be more frequent than in areas surrounding it. This will provide new insights into the evolution of a segment of the genome and aid in explaining how particular mutations are dispersed to numerous chromosome types. Second, study of additional beta-thalassemia genes from human populations not previously studied will provide new gene defects, some of which may yield further clues about RNA transcription and processing. In addition, some (e.g., the coding region substitutions that affect RNA processing) may allow identification of new mechanisms of gene dysfunction. Third, we need further refinement of prenatal diagnostic tests so that early, accurate, and simplified assessment of pregnancies at risk can be accomplished widely, particularly in those geographic regions where beta-thalassemia is especially prevalent.