Cloning of fibrinogen genes and their cDNA.

Cross-species hybridizations have enabled us to isolate and clone the gene for the beta chain of human fibrinogen. Highlights of the gene for the beta chain revealed by nucleotide sequence analyses, particularly in areas that have a direct bearing on defining the overall organization of the gene, have been presented. Nucleotide sequence determination has confirmed the presence of seven intervening sequences. The positions where several of these intervening sequences interrupt the coding region appear to be related to the functional domains of the polypeptide. A putative signal peptide has been identified. Studies on the cDNA for the human alpha chain indicate that the alpha chain polypeptide may be synthesized in a precursor form with a COOH-terminal extension of 15 amino acids as compared to the alpha chain present in the mature molecule found in plasma. We are in the process of isolating the genes for the alpha and gamma chains by a similar approach. We are hopeful that these studies will provide information as to how they are regulated and how they have undergone changes in the course of evolution.