We propose to use a combination of genetic, biochemical, and immunological approaches to examine Chinese hamster and human somatic cells and human-hamster hybrid cells containing human chromosome 21. Through such studies we hope to identify genes located on chromosome 21, to perform detailed mapping of these genes, and to determine the extent of their expression in normal and trisomy 21 cells. Since we have already assigned the locus of one enzyme involved in purine biosynthesis to chromosome 21, we intend to determine whether the genes for other enzymes in purine biosynthesis are located on this chromosome and whether elevation of purine synthesis, a condition which can be linked to mental deficiencies, is present in trisomy 21 cells. Also, we propose to determine what cell surface antigens, if any, are specified by human chromosome 21 and to develop antisera against them. After identifying several genes located on human chromosome 21 and developing methods for detecting their expression we plan to use procedures of radiation-induced chromosome breakage and DNA transfection to create a detailed genetic map of the chromosome.