There is an acute shortage of human functional loci mapped to specific chromosomal sites. Fewer than 1700 mapped genes (~3% of the total genome) are available to address basic genetic questions regarding the numbers and organization of genes, gene regulation, genetic mechanisms, and disease. The goal for this research continues to be the description of the human gene map, its association with disease, and its contribution to understanding genetic principles.
Specific aims for this period are three- fold: (1) generate detailed gene maps for three subregions of chromosome 11 associated with neoplasia and developmental disorders; (2) advance the gene map of all chromosomes; and (3) characterize mapped genetic disease. Several methodologies are proposed to isolate coding sequences from the WAGR 11p13 subregion, the PTH-pter subregion of p15.5, and the CD3-ETS1 subregion of q23.3. These regions have the potential to yield necessary information concerning genetic mechanisms and principles because of their location on chromosome 11 and the array of disorders associated with them. The description of the gene map for these three regions, with spatial and temporal expression profiles for genes, will enable us to address fundamental questions concerning gene number, the density of genes at the subtelomeric vs. more proximal locations, the relationship of CpG islands and genes, genome organization and gene regulation, and genomic imprinting. Candidate genes will be used to characterize the several disorders and chromosomal abnormalities mapped to these subregions, such as defining the number and type of genes involved in a contiguous gene syndrome, and the identification of genes disrupted or activated at translocation breakpoints or inactivated by other genetic mechanisms. Addressing these aspects for all chromosomes, we propose to advance all functional maps. These studies will map genes for genetic disease, neoplasia and those with defined biological function. These studies will allow us to correlate basic functions, disease, and genetic phenomena with map location.
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