Polymorphism of DNA Sequence in the β-Globin Gene Region

Abstract

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).

Variable Restriction Endonuclease Sites of Herpes Simplex Virus Type 1 Isolates from Encephalitic, Facial and Genital Lesions and Ganglia

“…RE cleavage site data can be (Nei & Li, 1979;Ewens et al, 1981) and have been used to investigate genetic relatedness in both viral DNA (Skare et al, 1975;Buchman et al, 1978;Lonsdale et al, 1979;Summers, 1980;Siddiqui et al, 1979;Callan, 1983 ;Heller et al, 1982) and non-viral DNA (Arnheim et al, 0022-1317/83/0000-5723 $02.00 © 1983 SGM s.M.I. CHANEY, K. G. WARREN AND J. H. SUBAK-SHARPE 1980; Kan et al, 1980;Brown, 1980;Antonarakis et al, 1982) because of the relative ease and reliability with which comparative data can be obtained.…”

Origin of cell populations after bone marrow transplantation. Analysis using DNA sequence polymorphisms.

“…These genetic markers have been widely used in the study and prenatal diagnosis of the hemoglobinopathies (18,19,25,26), and more recently in the analysis of other disorders (19,20,23 Table I. Preparative chemoradiation therapy varied according to the underlying disease and is also outlined in Table I.…”

A new polymorphism in the human beta-globin gene useful in antenatal diagnosis.

“…Polymorphisms of nucleic acid sequences within and adjacent to the f8-globin gene complex have recently afforded a new approach to the antenatal detection of f3-globin chain variants and /3-thalassemia (1T)1 (1)(2)(3)(4)(5). Kan and Dozy (1) initially reported a polymorphism in the DNA sequence for an Hpa I restriction endonuclease site 5 kilobases (kb) 3' to the f3-globin gene with the sickle mutation (#s).…”

“…Use of the Hind III polymorphism in conjunction with Hpa I has increased the feasibility of prenatal diagnosis to >80% in AS couples (4). Another polymorphic site 3' to the /3-gene is recognized by the enzyme Bam HI (5). A nucleotide change in the Bam HI site leads to the presence of a 22-kb fragment rather than the normal 8.3-kb fragment.…”

“…In a Sardinian population with a high incidence (originally reported as 9.3 kb) of f83-thalassemia, this polymorphism is potentially useful because the 22-kb fragment is associated with one-third of BA_genes, whereas the P0-thalassemia gene is only found with an 8.3-kb fragment (5).…”