Genetic mapping with SNP markers in Drosophila

Map-based positional cloning of Drosophila melanogaster genes is hampered b y both the time-consuming, error-prone nature of traditional methods for ge netic mapping and the difficulties in aligning the genetic and cytological maps with the genome sequence. The identification of sequence polymorphisms in the Drosophila genome will make it possible to map mutations directly t o the genome sequence with high accuracy and resolution. Here we report the identification of 7,223 single-nucleotide polymorphisms (SNPs) and 1,392 i nsertions/deletions (InDels) in common laboratory strains of Drosophila. Th ese sequence polymorphisms define a map of 787 autosomal marker loci with a resolution of 114 kb. We have established PCR product-length polymorphism (PLP) or restriction fragment-length polymorphism (RFLP) assays for 215 of these markers. We demonstrate the use of this map by delimiting two mutatio ns to intervals of 169 kb and 307 kb, respectively. Using a local high-dens ity SNP map, we also mapped a third mutation to a resolution of approximate ly 2 kb, sufficient to localize the mutation within a single gene. These me thods should accelerate the rate of positional cloning in Drosophila.