SNP and haplotype mapping for genetic analysis in the rat

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Abstract

The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies.

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Figure 1: Phylogenetic neighbor-net network constructed from 20,283 polymorphic positions genotyped in 167 laboratory rats.
Figure 2: Identified discrepancies between rat genome assembly and genetic maps.

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Acknowledgements

This work was supported by European Union grants LSGH-2004-005235 and LSHG-CT-2005-019015. We acknowledge funding from the National Genome Research Network of the German Ministry of Science and Education. We thank all of the technical staff of the Sequencing Technology Team at the RIKEN Genomic Sciences Center for their assistance. Part of this work was supported by the National BioResource Project of the Ministry of Education, Culture, Sports, Science and Technology of Japan. D.G. is supported by a Wellcome Trust Senior Fellowship in Basic Biomedical Science (057733/Z/99/A). M.-T.B. and D.G. acknowledge support from the Wellcome Cardiovascular Functional Genomics Initiative (066780/Z/01/Z). M. Pravenec is supported by the Howard Hughes Medical Institute and by the Grant Agency of the Czech Republic. M. Pravenec and V.K. are supported by grants from the Ministry of Education of the Czech Republic.

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Correspondence to Norbert Hubner.

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Supplementary Figures 1–7, Supplementary Tables 1–6, Supplementary Methods, Supplementary Note (PDF 3127 kb)

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