DELETION IN ERYTHROCYTE BAND-3 GENE IN MALARIA-RESISTANT SOUTHEAST-ASIAN OVALOCYTOSIS
DELETION IN ERYTHROCYTE BAND-3 GENE IN MALARIA-RESISTANT SOUTHEAST-ASIAN OVALOCYTOSIS
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DOI：
10.1073/pnas.88.24.11022
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
LIU, SC
中科院分区：
文献类型：
--
作者：
JAROLIM, P;PALEK, J;LIU, SC
东南亚卵泡细胞增多症 (SAO) 是一种遗传性疾病，在东南亚部分地区普遍存在。卵形红细胞坚硬，能抵抗各种疟原虫的侵袭。我们之前发现SAO的潜在缺陷涉及带3蛋白，即主要的跨膜蛋白，其结构和功能异常。我们现在报告了 SAO 中红细胞带 3 基因的两个连锁突变：(i) 密码子 400-408 的删除和 (ii) 密码子 56 的第一个碱基中的替换 A --> G，导致 Lys-56 被 Glu-56 替换。第一个缺陷导致带 3 的细胞质和膜域边界中的 9 个氨基酸缺失。在来自马来西亚、菲律宾和巴布亚新几内亚两个不相关沿海地区的所有 30 名卵细胞受试者中均检测到了这种缺陷，而在来自东南亚的所有 30 名对照者和来自美国的 20 名不同种族的受试者中均不存在这种缺陷。 Lys-56 --> Glu 替代同样在所有 SAO 受试者中被发现。然而，在 50 名对照受试者中的 5 名中也检测到了它，这表明它代表了连锁多态性。我们得出结论，带 3 基因中密码子 400-408 的删除构成了 SAO 的潜在分子缺陷。
Southeast Asian ovalocytosis (SAO) is a hereditary condition that is widespread in parts of Southeast Asia. The ovalocytic erythrocytes are rigid and resistant to invasion by various malarial parasites. We have previously found that the underlying defect in SAO involves band 3 protein, the major transmembrane protein, which has abnormal structure and function. We now report two linked mutations in the erythrocyte band 3 gene in SAO: (i) a deletion of codons 400-408 and (ii) a substitution, A --> G, in the first base of codon 56 leading to substitution of Lys-56 by Glu-56. The first defect leads to a deletion of nine amino acids in the boundary of cytoplasmic and membrane domains of band 3. This defect has been detected in all 30 ovalocytic subjects from Malaysia, the Philippines, and two unrelated coastal regions of Papua New Guinea, whereas it was absent in all 30 controls from Southeast Asia and 20 subjects of different ethnic origin from the United States. The Lys-56 --> Glu substitution has likewise been found in all SAO subjects. However, it has also been detected in 5 of the 50 control subjects, suggesting that it represents a linked polymorphism. We conclude that the deletion of codons 400-408 in the band 3 gene constitutes the underlying molecular defect in SAO.