INVERSIONS DISRUPTING THE FACTOR-VIII GENE ARE A COMMON-CAUSE OF SEVERE HEMOPHILIA-A
INVERSIONS DISRUPTING THE FACTOR-VIII GENE ARE A COMMON-CAUSE OF SEVERE HEMOPHILIA-A
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DOI：
10.1038/ng1193-236
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发表时间：
1993-11-01
期刊：
影响因子：
30.8
通讯作者：
GITSCHIER, J
中科院分区：
文献类型：
--
作者：
LAKICH, D;KAZAZIAN, HH;GITSCHIER, J
仅在一半以上的严重血友病患者中发现了因子基因的突变。为了解释这些未知的突变，我们提出了一个基于位于因子基因上游22号内含子的同源序列之间重组的可能性的模型。这样的重组将导致所有中间DNA的倒置和基因的破坏。我们提出了支持这一模型的证据，并描述了一种检测倒位的Southern印迹分析。这些发现对于在大约45%患有严重疾病的家庭中预测血友病A的基因应该是有价值的。
Mutations in the factor VIII gene have been discovered for barely more than half of the examined cases of severe haemophilia A. To account for the unidentified mutations, we propose a model based on the possibility of recombination between homologous sequences located in intron 22 and upstream of the factor VIII gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. We present evidence to support this model and describe a Southern blot assay that detects the inversion. These findings should be valuable for genetic prediction of haemophilia A in approximately 45% of families with severe disease.