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Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat

Item Type:Article
Title:Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat
Creators Name:Atanur, S.S. and Diaz, A.G. and Maratou, K. and Sarkis, A. and Rotival, M. and Game, L. and Tschannen, M.R. and Kaisaki, P.J. and Otto, G.W. and John Ma, M.C. and Keane, T.M. and Hummel, O. and Saar, K. and Chen, W. and Guryev, V. and Gopalakrishnan, K. and Garrett, M.R. and Joe, B. and Citterio, L. and Bianchi, G. and McBride, M. and Dominiczak, A. and Adams, D.J. and Serikawa, T. and Flicek, P. and Cuppen, E. and Hubner, N. and Petretto, E. and Gauguier, D. and Kwitek, A. and Jacob, H. and Aitman, T.J.
Abstract:Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and insulin resistance, along with their respective control strains. Altogether, we identified more than 13 million single-nucleotide variants, indels, and structural variants across these rat strains. Analysis of strain-specific selective sweeps and gene clusters implicated genes and pathways involved in cation transport, angiotensin production, and regulators of oxidative stress in the development of cardiovascular disease phenotypes in rats. Many of the rat loci that we identified overlap with previously mapped loci for related traits in humans, indicating the presence of shared pathways underlying these phenotypes in rats and humans. These data represent a step change in resources available for evolutionary analysis of complex traits in disease models.
Keywords:Animal Disease Models, Genome, Phenotype, Phylogeny, Single Nucleotide Polymorphism, Animals, Rats
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:154
Number:3
Page Range:691-703
Date:1 August 2013
Official Publication:https://doi.org/10.1016%2Fj.cell.2013.06.040
PubMed:View item in PubMed

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