Lie-Injo L E, Hassan K, Joishy S K, Lim M L
Am J Hematol. 1986 Jul;22(3):265-74. doi: 10.1002/ajh.2830220307.
The Indian rubber estate workers in Negri Sembilan, Malaysia, who originated from Orissa in India were found to have a high frequency of Hb S (Joishy SK, Hassan K: Clin Res 28:280, 1980). Unlike the usually severe clinical picture of sickle cell anemia seen in African and American blacks, the clinical picture of the disease in this population was mild and many have reached old age. We studied the leukocyte DNA of 12 patients with sickle cell anemia, ranging in age from 4 to 61 years and 30 sickle cell trait carriers, ranging in age from 7 to 63 years, for the presence of alpha-globin gene deletions by gene mapping according to Southern (Southern EM: J Mol Biol 98:503, 1975), using alpha- and zeta-globin gene probes obtained by nick translation of the alpha- and zeta-globin genes cloned into plasmid. All 12 sickle cell anemia patients were found to have alpha-thalassemia2 (alpha-thal2), either in the homozygous or heterozygous condition. Of the Hb S trait carriers, six did not have alpha-thal2 or alpha-thal1 and 24 had alpha-thal2 (15 heterozygous, 9 homozygous). Seven of these Hb S trait carriers with alpha-thal2 had an additional gene abnormality. Five of them had a fast-moving Eco RI fragment 5.6 kb long that hybridized with zeta-specific probe but not with alpha-specific probe. An unusual DNA pattern of a different type was further found in the other two. Bgl II restriction analysis showed that the alpha-thal2 was mostly of the rightward deletion alpha-thal1 genotype. None of the sickle cell anemia patients and Hb S trait carriers had deletion type alpha-thal1. The sickle cell anemia patients had very high levels of Hb F and low levels of Hb A2. The Hb S trait carriers with alpha-thal2 had relatively low levels of Hb S.
马来西亚森美兰州的印度橡胶园工人来自印度奥里萨邦，他们被发现携带血红蛋白S（Hb S）的频率很高（乔希SK，哈桑K：《临床研究》28：280，1980）。与非洲和美国黑人中通常所见的镰状细胞贫血严重临床症状不同，该人群中这种疾病的临床症状较为轻微，许多人已步入老年。我们研究了12例年龄在4至61岁的镰状细胞贫血患者以及30例年龄在7至63岁的镰状细胞性状携带者的白细胞DNA，通过根据萨瑟恩（萨瑟恩EM：《分子生物学杂志》98：503，1975）的基因定位法检测α-珠蛋白基因缺失情况，使用通过对克隆到质粒中的α-和ζ-珠蛋白基因进行切口平移获得的α-和ζ-珠蛋白基因探针。发现所有12例镰状细胞贫血患者均患有α-地中海贫血2（α-thal2），处于纯合或杂合状态。在Hb S性状携带者中，6例没有α-thal2或α-thal1，24例有α-thal2（15例杂合，9例纯合）。这些携带α-thal2的Hb S性状携带者中有7例存在额外的基因异常。其中5例有一个5.6 kb长的快速移动的Eco RI片段，它与ζ特异性探针杂交但不与α特异性探针杂交。另外两例中还发现了一种不同类型的异常DNA模式。Bgl II限制性分析表明，α-thal2大多为向右缺失的α-thal1基因型。镰状细胞贫血患者和Hb S性状携带者均未出现缺失型α-thal1。镰状细胞贫血患者的Hb F水平非常高，Hb A2水平很低。携带α-thal2的Hb S性状携带者的Hb S水平相对较低。
