In this paper we have tried to relate the salient features of gene structure, genomic organization, normal variation, and mutations affecting gene expression. The lessons learned from the normal beta-globin gene cluster and mutations producing beta-thalassemia should be greatly applicable to studies of other inherited diseases. As more and more gene probes become available which have relevance to the study of human disease, the striking extent of genetic heterogeneity producing single gene disorders of man will be illuminated.