Winship P R, Anson D S, Rizza C R, Brownlee G G
Nucleic Acids Res. 1984 Dec 11;12(23):8861-72. doi: 10.1093/nar/12.23.8861.
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.
除了已鉴定的凝血因子IX基因TaqI多态性（1,2）外，对正常人群进行了筛查，以寻找该基因中是否存在其他限制性片段长度多态性（RFLP）。发现了两个多态性位点，均位于因子IX基因内部TaqI多态性的6 kb范围内。其中一个多态性已被证明是由于限制性内切酶XmnI的特定识别位点的存在或缺失所致。另一个多态性表现为用HinfI或DdeI消化产生的片段模式差异，有两种等位基因形式，相差一个50 bp的插入DNA元件。序列分析表明，插入元件位于Z型DNA序列区域，该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，并且都已用于诊断B型血友病携带者状态。据估计，尽管这3个多态性位点之间存在连锁不平衡，但联合使用因子IX基因中的这些多态性，应该能够在大约66%的所有B型血友病家族中确定携带者状态。
