The goal of this project is to identify the chromosomal map position of the genes causing peripheral or von Recklinhausen's neurofibromatosis, bilateral acoustic or central neurofibromatosis and von Hippel-Lindau disease. The development of recombinant DNA technology has introduced to human genetics a vast new supply of polymorphic markers. These markers are detected as differences in the pattern of restriction enzyme cleavage of human DNA and hence have been termed restriction fragment length polymorphisms (RFLPs). The number of new RFLPs identified in the past few years has already far exceeded the 25-30 standard polymorphic protein markers typically used for genetic linkage studies. It will soon be possible to construct a complete genetic linkage map of the human genome using DNA markers representing all regions of all chromosomes. Our stragegy in this project will be to take DNA markers currently available and new markers as they are isolated and trace their inheritance in large disease pedigrees from these three phakomatoses. The data will be computer analyzed for significant coinheritance of each marker with the disease genes in question. The discovery of the DNA marker linked to one of these disease genes will allow the assignment of this disease defective locus to a particular human chromosome. Such a discovery would have profound implications for genetic counseling and patient management as well as for development of a better understanding and categorization of diseases comprising the phakomatoses. Ultimately the mapping of each of these genes may permit the application of chromosome specific cloning strategies to perform the isolation and characterization of the primary defects involved. An knowledge of the primary defect in each disorder could well lead to an effective therapy for these disorders.
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