Review articles in prestige journal Nature Genetics

Identification of single nucleotide polymorphisms and haplotype mapping in the rat

The laboratory rat is one of the most extensively studied model organisms and is the major animal model in the initial stages of drug development. The most commonly used inbred laboratory rat strains have originated from limited founder populations which exclusively have been derived from Rattus norvegicus and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation in the rat genome based on the discovery of almost 3 million novel SNPs. We then obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, the two largest existing rat recombinant inbred (RI) panels, and an intercross. Using 81% of these SNPs we constructed high density genetic maps, thereby creating a large dataset of fully characterized SNPs for disease gene mapping, applicable to any strain combination. Our data also characterise the population structure and illustrate the degree of linkage disequilibrium among the rat inbred strains. We provide a detailed SNP map and demonstrate its utility for QTL mapping studies, including the existing RI panels, as well as and in understanding the population genetics of this model for human disease.
K. Saar, A. Beck, M.-T. Bihoreau, E. Birney, D. Brocklebank, Y. Chen, E. Cuppen, S. Demonchy, J. Dopazo, P. Flicek, M. Foglio, A. Fujiyama, I. G. Gut, D. Gauguier, R. Guigo, V. Guryev, M. Heinig, O. Hummel, N. Jahn, S. Klages, V. Kren, M. Kube, H. Kuhl, T. Kuramoto, Y. Kuroki, D. Lechner, Y-A. Lee, N. Lopez-Bigas, G. M. Lathrop, T. Mashimo, I. Medina, R. Mott, G. Patone, J-A. Perrier-Cornet, M. Platzer, M. Pravenec, R. Reinhardt, Y. Sakaki, M. Schilhabel, H. Schulz, T. Serikawa, M. Shikhagaie, S. Tatsumoto, S. Taudien, A. Toyoda, B. Voigt, D. Zelenika, H. Zimdahl, N. Hubner: SNP and haplotype mapping for genetic analysis in the rat, Nature Genetics 40:560-566, 2008, IF=25.556

Author: pravenecbiomed.cas.cz
 

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