Labie D, Dunda-Belkhodja O, Rouabhi F, Pagnier J, Ragusa A, Nagel R L
Blood. 1985 Dec;66(6):1463-5.
To test the hypothesis advanced by Gilman and Huisman that the -158 site 5' to the G gamma gene determines the G gamma expression after the first 4 months of life, we have examined DNA from sickle cell anemia (SS) patients from Africa and beta-thalassemic homozygotes from Algeria. We find that the Xmnl site is strongly linked to the Senegal haplotype among SS patients, to haplotype IX (most probably identical to the Senegal haplotype), and to haplotype III among the Algerian thalassemics. Thalassemics with haplotypes I/I and V/V have no Xmnl site and low G gamma expression. In contrast, beta-thalassemia-associated haplotype II (also characterized by high G gamma expression) fails to exhibit the Xmnl site. We conclude that, although highly correlated, the -158 C----T substitution does not perfectly predict the presence of high G gamma expression. These findings also exclude the possibility that the Xmnl site is solely involved in the determination of high G gamma expression and suggest that either several different site substitutions in the area 5' to the gamma gene might have the same effect or that, alternatively, the Xmnl site and its surrounding area is not involved in G gamma expression and may be only in linkage disequilibrium with a controlling sequence elsewhere.
为了验证吉尔曼和休斯曼提出的假说，即位于Gγ基因5'端-158位点决定出生后前4个月后的Gγ表达，我们检测了来自非洲的镰状细胞贫血（SS）患者以及来自阿尔及利亚的β地中海贫血纯合子的DNA。我们发现，在SS患者中，XmnI位点与塞内加尔单倍型紧密连锁，在阿尔及利亚地中海贫血患者中，与单倍型IX（很可能与塞内加尔单倍型相同）以及单倍型III紧密连锁。具有单倍型I/I和V/V的地中海贫血患者没有XmnI位点且Gγ表达较低。相反，与β地中海贫血相关的单倍型II（也以高Gγ表达为特征）没有XmnI位点。我们得出结论，尽管-158 C→T替换与高Gγ表达高度相关，但并不能完美预测高Gγ表达的存在。这些发现也排除了XmnI位点单独参与决定高Gγ表达的可能性，并表明要么γ基因5'端区域的几种不同位点替换可能具有相同的效应，要么XmnI位点及其周围区域不参与Gγ表达，可能仅与其他地方的一个控制序列处于连锁不平衡状态。
