Using normal euploid cells in culture, we propose to continue research pertinent to X inactivation and control of cell phenotype. We will determine: 1) if the entire X chromosome is subject to inactivation by analyzing clones fromheterozygotes for X-linked variants; 2) the relationship between dose of autosomes and active X chromosomes in triploid (embryonic) cells; 3) if the silent X can be reactivated by fusion with chick cells or mouse blastocysts or in cells treated with mutagens; and 4) if DNA from the inactive X has unique properties by in situ hybridization with human metaphase chromosomes. We will carry out complementation analysis in search of genetical heterogeneity using heterokaryons of human cells from phenotypically similar inborn errors of metabolism. We will look for segregants from human intraspecific hybrids carrying multiple genetic markers as a means to detect 1) segregants and 2) somatic recombination. We will continue to develop the D-val selective system for epithelial cells which have D amino acid oxidase, an enzyme present only in differentiated cells, and to map this selctive marker using mouse-human hybrids.