Abstract : This project aims to collect NF1 patient DNAs required to identify neurofibroma burden modifier genes, to perform an allele association study for three classes of potential modifiers, and to evaluate more global approaches. Over four years we aim to collect 1200 DNAs from adult NF1 patients that represent the top and bottom 20% of dermal neurofibroma burden in various age cohorts. We will use these DNAs in a case-control allele association study, to test whether neurofibroma numerical variability reflects (1) allelic differences in genes that maintain genome stability; (2) differences in the NF1 gene itself or in closely linked genes; or (3) differences in genes involved in signaling between neurofibroma constituent cells. The Army Office of Regulatory Compliance took until February 2004 to sign an approval memorandum for this study and disallowed one of our major proposed routes of patient recruitment. Our major progress during the first year, in addition to obtaining regulatory approval, has been the implementation of a relational database of 990 potential modifier genes in the signaling category. Other effort has gone towards enrolling additional collaborators to make up for the disallowed recruitment route, and towards implementing more efficient methods of SNP genotyping.