ALPHA-GLOBIN GENE ORGANIZATION IN BLACKS PRECLUDES THE SEVERE FORM OF ALPHA-THALASSEMIA
ALPHA-GLOBIN GENE ORGANIZATION IN BLACKS PRECLUDES THE SEVERE FORM OF ALPHA-THALASSEMIA
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DOI：
10.1038/280605a0
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发表时间：
1979-01-01
期刊：
影响因子：
64.8
通讯作者：
KOENIG, HM
中科院分区：
文献类型：
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作者：
DOZY, AM;KAN, YW;KOENIG, HM
在大多数人群中，α-珠蛋白结构基因位点是重复的，因此每个二倍体细胞包含四个副本的 α-珠蛋白基因1-3。 α-地中海贫血是一种 α-珠蛋白链合成的遗传性疾病，最常见的分子病变是由于 α-珠蛋白基因 4-7 的缺失。在亚洲人群中，四种主要的α-地中海贫血综合征的临床严重程度逐渐增加：（1）无临床表现的沉默携带者状态（α-地中海贫血-2）； (2)α-地中海贫血性状(α-地中海贫血-1)，其特征是红细胞小，但贫血很少或不贫血； (3)血红蛋白-H病，表现为溶血性贫血； (4) 纯合性α-地中海贫血，其中受影响的胎儿在足月或足月前后死于胎儿水肿。这四种综合征是由于α-珠蛋白基因的一个或全部四个拷贝的缺失所致。在这项研究中，我们描述了非洲裔人群的α-地中海贫血特征。血红蛋白筛查计划表明，α-地中海贫血发生在黑人群体中8-10。最近，我们通过互补 DNA-DNA 杂交证明，在具有临床明确的 α-地中海贫血特征的黑人个体中，四个正常 α-珠蛋白基因中的两个被删除11。然而，在该人群中，血红蛋白-H 病很少见，并且从未发现纯合 α-地中海贫血12,13。在这项研究中，我们使用了 Southern14 的限制性内切酶作图技术来描绘 α-珠蛋白基因缺失的性质。
IN most human populations, theα-globin structural gene loci are duplicated so that each diploid cell contains four copies ofα-globin genes1–3. Inα-thalassaemia, a hereditary disorder ofα-globin chain synthesis, the most common molecular lesion is due to the deletion of theα-globin genes4–7. In the Asian population, four mainα-thalassaemia syndromes of increasing clinical severity are recognised: (1) the silent carrier state (α-thalassaemia-2) with no clinical manifestation; (2)α-thalassaemia trait (α-thalassaemia-1), characterised by microcytic red blood cells but little or no anaemia; (3) haemoglobin-H disease, which manifests as haemolytic anaemia; and (4) homozygousα-thalassaemia, in which the afflicted fetus dies at or around term from hydrops fetalis. These four syndromes are due to the deletion of from one to all four copies of theα-globin genes. In this study, we have characterisedα-thalassaemia in people of African origin. Haemoglobin screening programmes have shown thatα-thalassaemia occurs in the black population8–10. Recently we have demonstrated by complementary DNA–DNA hybridisation that in black individuals with clinically well definedα-thalassaemia trait, two of the four normalα-globin genes were deleted11. However, in this population, haemoglobin-H disease is rare and homozygousα-thalassaemia has never been found12,13. For this study we have used the restriction endonuclease mapping technique of Southern14to delineate the nature of the deletion of theα-globin genes.