COMMON HAPLOTYPE DEPENDENCY OF HIGH-G-GAMMA-GLOBIN GENE-EXPRESSION AND HIGH HB F-LEVELS IN BETA-THALASSEMIA AND SICKLE-CELL ANEMIA PATIENTS
COMMON HAPLOTYPE DEPENDENCY OF HIGH-G-GAMMA-GLOBIN GENE-EXPRESSION AND HIGH HB F-LEVELS IN BETA-THALASSEMIA AND SICKLE-CELL ANEMIA PATIENTS
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DOI：
10.1073/pnas.82.7.2111
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
NAGEL, RL
中科院分区：
文献类型：
--
作者：
LABIE, D;PAGNIER, J;NAGEL, RL
纯合子的度量。对阿尔及利亚42例地中海贫血患者和塞内加尔和贝宁34例镰状细胞性贫血患者进行了研究，确定了单倍型、血红蛋白F和g . γ .-球蛋白/ a. γ之间的关系。球蛋白比率。由于亲缘关系（阿尔及利亚）和地理上的同质性（西非），所选择的种群具有高频率的单倍型纯合子。在度量。-地中海贫血患者，单倍型纯合子和杂合子中的单倍型IX，杂合子中的单倍型III，镰状细胞性贫血患者中的塞内加尔单倍型都与高g . γ有关。球蛋白表达。单倍型IX和塞内加尔有高的Hb F水平，而单倍型III没有。所有这些单倍型在。γ中有一个共同的亚单倍型（+-+++）。-珠蛋白基因区。单倍型IX， III和塞内加尔镰状细胞性贫血患者表现出血液学改善的疾病。地中海贫血患者的单倍型I、V和A也有一个共同的亚单倍型（-----），镰状细胞性贫血患者的贝宁亚单倍型（- ++-）都与低g . γ有关。-珠蛋白和低血红蛋白F水平。G.gamma低。-珠蛋白在成人中的表达与两种单倍型相关，而这两种单倍型在地中海贫血和镰状细胞性贫血患者中并不常见。高g的行列式。在这两种疾病中-珠蛋白的表达与常见的和遗传上显性的亚单倍型相关。总血红蛋白F水平，不像高g。-珠蛋白的表达与单倍型有关，而与亚单倍型无关，从而分离了两种遗传效应。
Homozygous .beta.-thalassemia patients (42) from Algeria and 34 sickle cell anemia patients from Senegal and Benin were studied, determining the relationship between haplotypes, Hb F, and G.gamma.-globin/A.gamma.-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). In .beta.-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozygotes, and the Senegal haplotype in sickle cell anemia patients are all linked to high G.gamma.-globin expression. Haplotypes IX and Senegal, but not haplotype III, have high Hb F levels. All of these haplotype have a common subhaplotype (+-+++) in the .gamma.-globin gene region. Haplotypes IX, III and Senegalese sickle cell anemia patients exhibit hematological amelioration of their disease. Haplotypes I, V and A in thalassemia patients, which also have a common subhaplotype (-----), and the Benin subhaplotype (--++-) in sickle cell anemia patients are all associataed with low G.gamma.-globin and low Hb F levels. Low G.gamma.-globin expression in the adult is associated with 2 haplotypes that are not common between thalassemia and sickle cell anemia patients. The determinant for high G.gamma.-globin expression is haplotype-linked to common and genetically dominant subhaplotypes in the 2 diseases. The total Hb F level, unlike the high G.gamma.-globin expression is linked to haplotypes but not to subhaplotypes, thus dissociating the 2 genetic effects.