Key result
Shotgun sequencing of a single wild rat identified 485 SNPs, of which 84% were also polymorphic in 36 commonly used laboratory rat strains, demonstrating an efficient SNP discovery approach.
Shotgun sequencing in a wild rat sample followed by genotyping in laboratory strains is an efficient approach for SNP discovery in rats.
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May streamline rat SNP discovery; leaves open scalability and functional validation in broader models.
BACKGROUND: The laboratory rat (Rattus norvegicus) is an important model for studying many aspects of human health and disease. Detailed knowledge on genetic variation between strains is important from a biomedical, particularly pharmacogenetic point of view and useful for marker selection for genetic cloning and association studies. RESULTS: We show that Single Nucleotide Polymorphisms (SNPs) in commonly used rat strains are surprisingly well represented in wild rat isolates. Shotgun sequencing of 814 Kbp in one wild rat resulted in the identification of 485 SNPs as compared with the Brown Norway genome sequence. Genotyping 36 commonly used inbred rat strains showed that 84% of these alleles are also polymorphic in a representative set of laboratory rat strains. CONCLUSION: We postulate that shotgun sequencing in a wild rat sample and subsequent genotyping in multiple laboratory or domesticated strains rather than direct shotgun sequencing of multiple strains, could be the most efficient SNP discovery approach. For the rat, laboratory strains still harbor a large portion of the haplotypes present in wild isolates, suggesting a relatively recent common origin and supporting the idea that rat inbred strains, in contrast to mouse inbred strains, originate from a single species, R. norvegicus.
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Smits et al. (2005) studied Genetic variation in Rattus norvegicus (n=39). Wild rat-based shotgun sequencing and genotyping vs. Brown Norway rat genome sequence was evaluated on Identification of shared SNPs between wild and laboratory rats. Shotgun sequencing of a single wild rat identified 485 SNPs, of which 84% were also polymorphic in 36 commonly used laboratory rat strains, demonstrating an efficient SNP discovery approach.
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