We propose to use recombinant DNA technology to study the structure, chromosomal arrangement, and for some tissues, the site of transcription, of genes which encode polypeptides related to insulin. We plan to isolate double-stranded cDNA (ds-cDNA) clones which encode these polypeptides and then use these clones to isolate the chromosomal sequences from the available cloned libraries of human and mouse sequences. To localize the cells in which these sequences are transcribed, we will use the ds-cDNA libraries which we have prepared from RNA from human fetal and adult tissues. Initially, we will use a clone (which we have isolated) encoding human insulin to screen the ds-cDNA clones. The clones selected in the initial screen will be compared by restriction enzyme analysis, DNA sequencing and by cross-hybridization. These clones can be used to select other ds-cDNA clones as well as to select chromosomal clones. We are interested in finding out if the sequences we detect in human fetal tissues, particularly the brain, correspond to any of the characterized insulin-like growth factors (somatomedins). The total number of somatomedins is not known. We would like to know which, if any, of these genes are closely linked to each other or to the gene encoding insulin. We would also like to know whether all of these genes have retained a similar intron-exon arrangement or whether differences in this arrangement have occurred as this family of related genes has diverged. Cloned sequences should also facilitate the study of the biological action of these proteins since the cloned sequences could be modified to allow the synthesis of these proteins by the bacterial host. The protein would then be available for the generation of antibodies, and for biological studies. The goals of our work are to gain information about the structure and arrangement of a set of genes which are related to each other by sequence and which presumably arose from a common ancestor. By studying the structure of the insulin related genes, we expect to gain information which will be of interest not only for the general understanding of gene expression but which will be of use in the study of human growth and development.