Kazazian H H, Phillips J A, Boehm C D, Vik T A, Mahoney M J, Ritchey A K
Blood. 1980 Nov;56(5):926-30.
In order to assess the applicability of multiple restriction endonuclease analyses of amniocyte DNA to the prenatal diagnosis of beta-thalassemias in general, we studied 12 consecutive couples at risk. DNA of both members of the 12 couples and a previous offspring of each was analyzed for the presence of 4 polymorphic restriction endonuclease sites: the Hpa I site 3' to the beta-globin gene, the Hind III site in the G gamma gene, the Hind III site in the A gamma gene, and the Bam HI site 3' to the beta-gene. Linkage disequilibrium between these sites and beta A or beta thal genes was not found, presumably due to the heterogeneity of beta thal genes. However, the high frequency of polymorphism at these sites allowed differentiation of beta A-bearing chromosomes from beta thal or beta S-bearing chromosomes in both members of 6 couples. In these couples, complete prenatal diagnosis by linkage analysis of amniocyte DNA would be possible. In the remaining 6 couples, beta A and beta thal chromosomes could be discriminated in one member. In about 50% of the pregnancies of these couples, exclusion of beta-thalassemia is possible by this analysis. These data suggest that when linkage analysis of polymorphic restriction endonuclease sites is carried out, prenatal diagnosis of beta-thalassemia states can be accomplished by amniocentesis alone in 75% of pregnancies at risk.
为了总体评估羊水细胞DNA的多种限制性内切酶分析在β地中海贫血产前诊断中的适用性，我们研究了连续12对有风险的夫妇。对这12对夫妇双方及其每个家庭之前生育的一个后代的DNA进行分析，检测4个多态性限制性内切酶位点的存在情况：β珠蛋白基因3'端的Hpa I位点、Gγ基因中的Hind III位点、Aγ基因中的Hind III位点以及β基因3'端的Bam HI位点。未发现这些位点与βA或β地中海贫血基因之间存在连锁不平衡，推测这是由于β地中海贫血基因的异质性所致。然而，这些位点的高多态性频率使得6对夫妇双方的携带βA的染色体与携带β地中海贫血或βS的染色体得以区分。在这些夫妇中，通过羊水细胞DNA的连锁分析进行完全产前诊断是可行的。在其余6对夫妇中，仅能在一方中区分βA和β地中海贫血染色体。在这些夫妇约50%的妊娠中，通过这种分析有可能排除β地中海贫血。这些数据表明，当进行多态性限制性内切酶位点的连锁分析时，在75%有风险的妊娠中，仅通过羊膜穿刺术就能完成β地中海贫血状态的产前诊断。
