This project is designed to (a) elucidate human genes which are important in the control of gene expression and to (b) determine the genetic organization of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. These studies involve the genetic characterization of a group of acid hydrolases associated with lysomones. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay Sachs disease, Sandhoff-Jatzhewitz disease, metachromatic leukodystrophy, generalized gangliosidosis, Fabry's disease, and fucosidosis. These studies are deigned to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies which result in fatal childhood diseases and, hopefully, to aid in the diagnosis, prenatal detection, and treatment of lysosomal storage diseases. It is anticipated that such information will be necessary for the construction of models of lysosomal biogenesis and regulation which are imporant aspects of human development. Proliferating man-mouse somatic cell hybrids are particularly suited for this study since human chromosomes, but not mouse chromosomes, are lost which provides the mechanism to identify human genes and linkage relationships. The mapping of human genes to linkage groups requires a large number of markers. It is planned to increase our present catalogue from about 40 human enzyme markers to 60 markers by optimizing procedures for new enzymes, ribosomal proteins, and membrane proteins. These data will increase the chances of placing genes associated with development on each human chromosome.
NIH ExPorter
NIH ExPorter