Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p and 6q by the regressive approach
Dissecting the loci controlling fetal haemoglobin production on chromosomes 11p and 6q by the regressive approach
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DOI：
10.1038/ng0196-58
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发表时间：
1996-01-01
期刊：
影响因子：
30.8
通讯作者：
Thein, SL
中科院分区：
文献类型：
--
作者：
Craig, JE;Rochette, J;Thein, SL
在胚胎、胎儿和成年过程中产生的血红蛋白(Hb)类型的变化，已经成为理解人类基因发育调节的一个范例。基因决定的胎儿Hb合成的持久性对全球最常见的单基因疾病--β地中海贫血症和镰状细胞性贫血--有改善作用。寻找控制胎儿Hb产生水平的假定基因(S)一直是极其困难的，因为这一性状可能受到几个因素的影响。我们研究了一个遗传性持续性胎儿血红蛋白(HPFH)家族。利用遗传作图策略和同时考虑几个遗传因素影响的统计方法，我们证明了除了染色体11p上的两个因素(β地中海贫血症和XmanI-(G)Gamma位点)外，还有第三个主要的遗传决定因素位于染色体6q上，导致胎儿Hb的产生。
The changes in the type of haemoglobin (Hb) produced during embryonic, fetal and adult life, have served as a paradigm for understanding the developmental regulation of human genes. A genetically determined persistence of fetal Hb synthesis has an ameliorating effect on beta thalassaemia and sickle cell anaemia, globally the commonest single gene disorders. The search for the putative gene(s) controlling the level of fetal Hb production has been extremely difficult because this trait may be influenced by several factors. We have studied a large kindred with hereditary persistence of fetal haemoglobin (HPFH). Using a genetic mapping strategy and statistical methods that account simultaneously for the effects of several genetic factors, we have demonstrated that in addition to the two factors (beta thalassaemia and Xmn I-(G) gamma site) on chromosome 11p, there is a third major genetic determinant for fetal Hb production localized on chromosome 6q.