HETEROGENEITY OF DNA FRAGMENTS ASSOCIATED WITH THE SICKLE-GLOBIN GENE

The genetic polymorphism associated with the sickle-cell (.beta.S) gene involves an alteration of the DNA sequence 3'' to the .beta.-globin gene as detected with the restriction endonuclease, Hpa I. In normal individuals, the .beta.-globin gene is contained within a DNA fragment of 7.6 kilobases (kb), but 87% of individuals with sickle-cell anemia were reported to have the .beta.s-gene associated with a 13.0-kb Hpa I fragment. This polymorphism was studied in 31 New York black individuals homozygous for sickle-cell anemia to ascertain its genetic and biochemical significance and to evaluate its potential use in the prenatal diagnosis of sickle-cell disease. Results showed only a 58% association of the .beta.s-gene and the 13.0-kb Hpa I fragment, as well as the presence of additional variants involving the Hpa I site. In addition, the 13.0-kb fragment was also associated with the .beta.c- and .beta.A-genes. The Hpa I polymorphism probably represents a change in DNA not specifically associated with the .beta.S-gene, and appears to antedate the .beta.s- and .beta.c-mutations.