MOLECULAR BASIS FOR FACTOR X DEFICIENCY

当前提案的目标是定义导致 人类因子X缺乏症。正常人的核苷酸多态现象 患有凝血因子X缺乏症的个人和患者 通过限制性内切酶分析和RNA：DNA鉴定 混合分析。将对它们进行比较，以区分突变 与疾病相关的基因从正常的多态到特殊的多态。突变型 等位基因将通过家系研究来确定。不可能的突变 通过克隆和测序的方法对上述方法进行鉴定 凝血因子X缺陷者的人类凝血因子X基因及其比较 它们具有正常的因子X基因序列。克隆将会完成 通过使用波长矢量。核苷酸序列将由MAXAM建立 和Gilbert法以及双脱氧测序法进行了分析 通过各种计算机程序。在明确确定突变后 与疾病相关的我们将确定哪些核苷酸发生了变化 通过功能分析，实际上是导致这种疾病的病因。

The objective of the current proposal is to define mutations causing the human factor X deficiency. The nucleotide polymorphisms in normal individuals and patients suffering from factor X deficiency will be identified by restriction endonuclease analysis as well as by the RNA:DNA hybrid analysis. They will be compared to distinguish the mutations specifically related to the disease from the normal polymorphisms. Mutant alleles will be identified by family studies. Mutations which cannot be identified by the above methods will be detected by cloning and sequencing the human factor X genes from factor X deficient individuals and comparing them with the normal factor X gene sequences. Cloning will be accomplished by using lambda vectors. Nucleotide sequences will be established by Maxam and Gilbert method as well as by the dideoxy sequencing method and analysed by various computer programs. After identifying the mutations specifically related to the disease we will determine which of the nucleotide changes are actually etiologic in producing the disease by functional analysis.