Feldenzer J, Mears J G, Burns A L, Natta C, Bank A
J Clin Invest. 1979 Sep;64(3):751-5. doi: 10.1172/JCI109519.
We have examined the genetic polymorphism previously reported to be associated with the sickle-cell (beta s) gene. The polymorphism 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), whereas 87% of individuals with sickle-cell anemia have been reported to have the beta s-gene associated with a 13.0-kb Hpa I fragment. We have studied this polymorphism 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. Our results show 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 is also found associated with the beta c- and beta A-genes. Thus, 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.
我们研究了先前报道的与镰状细胞（βs）基因相关的遗传多态性。这种多态性涉及用限制性内切酶Hpa I检测到的β珠蛋白基因3'端DNA序列的改变。在正常个体中，β珠蛋白基因包含在一个7.6千碱基（kb）的DNA片段中，而据报道，87%的镰状细胞贫血患者的βs基因与一个13.0 kb的Hpa I片段相关。我们对31名镰状细胞贫血纯合子的纽约黑人个体研究了这种多态性，以确定其遗传和生化意义，并评估其在镰状细胞病产前诊断中的潜在用途。我们的结果显示，βs基因与13.0 kb的Hpa I片段之间的关联仅为58%，并且还存在涉及Hpa I位点的其他变体。此外，还发现13.0 kb的片段与βc和βA基因相关。因此，Hpa I多态性可能代表了一种并非与βs基因特异性相关的DNA变化，并且似乎早于βs和βc突变。
