IDENTIFICATION AND MAPPING OF TYPE-1 NEUROFIBROMATOSIS (NF1) HOMOLOGOUS LOCI

During the establishment of a YAC contig for the type 1 neurofibromato sis (NF1) region on human chromosome 17q11.2, several YAC clones were isolated which originated from a different chromosome but which retain ed strong homology to NF1 coding regions (Marchuk et al., 1992). Fluor escence in situ hybridization (FISH) using these clones has identified NF1-homologous loci on several human chromosomes, including 2, 14, 15 , 21, and 22. PCR amplification using primers originally designed to a mplify NF1 exons has confirmed these chromosome localizations and, in addition, has revealed NF1-homologous sequences on chromosomes 12 and 20. Sequence analysis of the amplified products has demonstrated that (1) most of these loci have > 90% identity with NF1 sequences; (2) mos t of these loci represent nonprocessed pseudogenes; and (3) for the ch romosome 12 locus, the two described regions of homology with NF1 have open reading frames. Finally, we have identified two novel alpha-sate llite DNA repeat units in proximity to NF1-homologous sequences on chr omosome 14. Their association suggests a mechanism for dispersion of t he NF1-homologous loci based on alpha-satellite-mediated exchange betw een nonhomologous chromosomes.