This application describes a proposed study of a region of chromosome 11, distal 11p12-proximal 11p14, all or part of which is characteristically deleted in the WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies and mental retardation). A nearly complete link-up long range restriction map of 11p13-proximal 11p14, encompassing at least 9.8 megabases of DNA, has been developed with pulse field gel electrophoresis and 24 new DNA probes for the WAGR deletion regions, together with 3 reference loci (catalase, beta subunit of follicle stimulating hormone and a hepatitis B virus integration site). With a complete long range restriction map of the WAGR deletion region as a framework, the chromosomal and molecular environments of multiple WAGR and AGR deletion breakpoints will be analyzed to identify sequences of architectural features specific to this class of chromosome rearrangements and important for their formation; the locations, environment and relationships within a small deletion subregion of the loci for Wilms tumor (WT), aniridia (AN) and the GU anomalies of the syndrome determined; and a second subregion likely responsible for mental retardation characterized. Using translocation breakpoints to identify DNA probes adjacent to or within the AN and GU loci, and deletions in the case of the WT locus, these genes will be sought for molecular analysis of their structure and function. In addition, the more than 185 DNA probes for regions of chromosome 11 other than the WAGR deletion region, will be used, together with other investigators, for development of an interlocking physical and linkage map of the chromosome.
