STUDIES OF NORMAL AND ABNORMAL HUMAN FACTOR 1X GENES

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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.