STUDIES OF NORMAL AND ABNORMAL HUMAN FACTOR 1X GENES

正常和异常人类因素 1X 基因的研究

• 批准号: 3354944
• 负责人: KOTOKU KURACHI
• 金额: $ 4.86万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354944
• 关键词: DNA; autosomal recessive trait; biological polymorphism; coagulation factor IX; complementary DNA; congenital blood protein disorder; electron microscopy; electrophoresis; hemophilia B; human tissue; messenger RNA; molecular cloning; molecular pathology; nucleic acid sequence; population genetics

Human factor IX (Christmas factor) is a single-chain glycoprotein (Mr = 56,000) that participates in the middle phase of blood coagulation. Factor IX deficiency (Christmas disease or hemophilia B) is a hereditary disorder caused by an abnormal factor IX gene. In order to understand the mechanism of this hereditary disease, we propose to study the normal and abnormal human factor IX genes on a molecular basis. Firstly, we plan to elucidate the organization and the complete DNA sequence for the normal gene. A genomic clone for the normal factor IX gene has already been isolated and a sequence analysis is currently in progress. The entire organization of the gene for factor IX will be established by a nucleotide sequence study in combination with an electron microscopic analysis of the heteroduplex molecules of the gene DNA with its cDNA or mRNA. Secondly, we plan to clone a number of abnormal factor IX genes and characterize them as to their DNA sequences in order to establish a mechanism of the disorder. Thirdly, we will analyze a number of the normal and abnormal genes in an attempt to find a restriction fragment unique to polymorphism(s) or abnormal gene(s). This finding may enable us to establish a fast and reliable prenatal diagnosis for factor IX deficiency.

人为因素IX（圣诞节因素）是单链糖蛋白（MR = 56,000）参与血液凝结的中间阶段。 因素 IX缺乏症（圣诞节疾病或血友病B）是一种遗传疾病 由异常因子IX基因引起。 为了理解机制 在这种遗传性疾病中，我们建议研究正常和异常 人类因子IX基因的分子基因。 首先，我们计划阐明 正常基因的组织和完整的DNA序列。 一个 正常因子IX基因的基因组克隆已经分离出来，A 序列分析目前正在进行中。 整个组织 第IX因子的基因将通过核苷酸序列研究建立 结合杂化的电子显微镜分析 基因DNA的分子和其cDNA或mRNA。 其次，我们计划 克隆许多异常因子IX基因，并将其表征为 它们的DNA序列是为了建立疾病的机制。 第三，我们将分析许多正常基因和异常基因 尝试找到多态性独有的限制片段或 异常基因。 这一发现可能使我们能够快速建立 因子IX缺乏症的可靠产前诊断。