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Genetic mapping with SNP markers in Drosophila

Abstract

Map-based positional cloning of Drosophila melanogaster genes is hampered by both the time-consuming, error-prone nature of traditional methods for genetic 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 to the genome sequence with high accuracy and resolution. Here we report the identification of 7,223 single-nucleotide polymorphisms (SNPs) and 1,392 insertions/deletions (InDels) in common laboratory strains of Drosophila. These 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 mutations to intervals of 169 kb and 307 kb, respectively. Using a local high-density SNP map, we also mapped a third mutation to a resolution of approximately 2 kb, sufficient to localize the mutation within a single gene. These methods should accelerate the rate of positional cloning in Drosophila.

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Figure 1: Classes and distribution of sequence polymorphisms in the Drosophila genome.
Figure 2: Polymorphism map of FRT versus EP strains.
Figure 3: Genotypes of additional useful laboratory strains.
Figure 4: Genetic mapping with SNP markers.
Figure 5: High-resolution mapping.

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Acknowledgements

We thank F. Eisenhaber and S. Maurer-Stroh for providing assistance in bioinformatics, A. Graf for technical assistance and M. Hohl and I. Botto for DNA sequencing. We are also grateful to the Berkeley Drosophila Genome Project, Celera Genomics and FlyBase for providing the wealth of resources that made this project possible. This work was funded by Boehringer Ingelheim GmbH.

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Correspondence to Barry J. Dickson.

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Berger, J., Suzuki, T., Senti, KA. et al. Genetic mapping with SNP markers in Drosophila. Nat Genet 29, 475–481 (2001). https://doi.org/10.1038/ng773

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