Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms.
Carrier detection in haemophilia B using two further intragenic restriction fragment length polymorphisms.
复制标题
使用两个进一步的基因内限制性片段长度多态性检测 B 型血友病的携带者。
作者：
P. Winship;D. Anson;C. Rizza;G. Brownlee
除了已经表征的TaqI多态性外，还对正常人群中凝血因子IX基因中存在的其他限制性片段长度多态性（RFLP）进行了筛查（1，2）。两个多态性位点被发现，都在6 Kb内的因子IX基因体内的TaqI多态性。其中一种多态性已被证明是由于限制酶XmnI的特定识别位点的存在或不存在。另一个，可视化为通过用HinfI或DdeI消化产生的片段模式的差异，具有两种等位基因形式，其不同之处在于插入DNA的50 bp元件。序列分析表明，插入的元件位于Z型DNA序列的区域中，插入代表两侧侧翼序列的重复。这两种多态性以简单的孟德尔方式遗传，并且都被用于诊断血友病B携带者状态。据估计，尽管3个多态性位点之间存在连锁不平衡，但在因子IX基因中这些多态性的联合使用应能在约66%的所有血友病B家族中确定携带者状态。
A normal human population has been screened for the existence of further restriction fragment length polymorphisms (RFLPs) in the clotting factor IX gene in addition to the TaqI polymorphism already characterised (1,2). Two polymorphic loci were found, both within 6 Kb of the TaqI polymorphism within the body of the factor IX gene. One of the polymorphisms has been shown to be due to either the presence or absence of a particular recognition site for the restriction enzyme XmnI. The other, visualised as a difference in fragment pattern produced by digestion with either HinfI or DdeI, has two allelic forms differing by a 50 bp element of inserted DNA. Sequence analysis has shown the inserted element to be in a region of Z type DNA sequence, the insertion representing a duplication of flanking sequence on either side. The two polymorphisms are inherited in simple Mendelian fashion and have both been used to diagnose haemophilia B carrier status. It is estimated that the combined use of these polymorphisms in the factor IX gene, despite linkage disequilibrium between the 3 polymorphic loci, should enable carrier status to be determined in approximately 66% of all haemophilia B families.