MOLECULAR BASIS FOR FACTOR X DEFICIENCY

当前提案的目的是定义导致 人类X因子缺乏症 基因多态性在正常人中的分布 患有X因子缺乏症的个体和患者将被 通过限制性内切酶分析以及通过RNA：DNA 混合分析 它们将被比较以区分突变 与正常的多态性特异性相关的疾病。 突变体 等位基因将通过家族研究来鉴定。 突变不能 将通过克隆和测序检测通过上述方法鉴定的 人因子X基因从因子X缺陷个体和比较 他们的X因子基因序列正常 克隆将完成 通过使用lambda向量。 将由Maxam确定核苷酸序列 和吉尔伯特法以及双脱氧测序法进行分析 通过各种计算机程序。 在明确识别出突变后 我们将确定哪些核苷酸发生了变化 实际上是通过功能分析产生疾病的病因。

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.