Rapid Mapping of Zebrafish Mutations With SNPs and Oligonucleotide Microarrays

Abstract

Large-scale genetic screens in zebrafish have identified thousands of mutations in hundreds of essential genes. The genetic mapping of these mutations is necessary to link DNA sequences to the gene functions defined by mutant phenotypes. Here, we report two advances that will accelerate the mapping of zebrafish mutations: (1) The construction of a first generation single nucleotide polymorphism (SNP) map of the zebrafish genome comprising 2035 SNPs and 178 small insertions/deletions, and (2) the development of a method for mapping mutations in which hundreds of SNPs can be scored in parallel with an oligonucleotide microarray. We have demonstrated the utility of the microarray technique in crosses with haploid and diploid embryos by mapping two known mutations to their previously identified locations. We have also used this approach to localize four previously unmapped mutations. We expect that mapping with SNPs and oligonucleotide microarrays will accelerate the molecular analysis of zebrafish mutations.[Supplemental material is available online atwww.genome.org. The sequence data described in this paper have been submitted to dbSNP under accession nos. 5103507–5105537. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: J. Postlethwait, C.-B. Chien, C. Kimmel, L. Maves, and M. Westerfield.]