Polymorphism of DNA Sequence in the β-Globin Gene Region

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Abstract
We used a restriction endonuclease to analyze the β-thalassemia gene in Sardinia. When we digested human DNA with the restriction enzyme Bam HI, the β-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 β-globin gene resulted in a different fragment, 22 kb in length, which contained the 3′ portion of the β-globin gene. In Sardinians without β-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 β0-thalassemia genes were associated exclusively with the 9.3-kb fragment. Thus, the β0-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 β0-thalassemia in Sardinia, since demonstration of the 22.0-kb fragment would indicate the normal β0-globin genotype and exclude the β0-thalassemia lesion on that chromosome. (N Engl J Med 302:185–188, 1980)