Polymorphism of DNA sequence in the beta-globin gene region. Application to prenatal diagnosis of beta 0 thalassemia in Sardinia.

We used a restriction endonuclease to analyze the beta-thalassemia gene in Sardinia. When we digested human DNA with the restriction enzyme Bam HI, the beta-globin gene split into a 5' portion contained in a fragment of DNA 1.8 kb in length and a 3' portion in a fragment 9.3 kb in length. In some subjects, a variation in the nucleotide sequence affecting the site recognized by this enzyme on the 3' side of the beta-globin gene resulted in a different fragment, 22 kb in length, which contained the 3' portion of the beta-globin gene. In Sardinians without beta-thalassemia, the frequency of the 9.3-kb fragment was 0.67, and that of the 22-kb fragment was 0.33. In contrast, all the beta 0-thalassemia genes were associated exclusively with the 9.3-kb fragment. Thus, the beta 0-thalassemia lesion in Sardinians apparently arose on a chromosome that had the 9.3-kb Bam HI fragment. This observation can be used in prenatal diagnosis of beta 0-thalassemia in Sardina, since demonstration of the 22.0-kb fragment would indicate the normal beta-globin genotype and exclude the beta 0-thalassemia lesion on that chromosome. (N Engl J Med 302:185-188, 1980).