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Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat.

Authors: Atanur, SS  Diaz, AG  Maratou, K  Sarkis, A  Rotival, M  Game, L  Tschannen, MR  Kaisaki, PJ  Otto, GW  John Ma, MC  Keane, TM  Hummel, O  Saar, K  Chen, W  Guryev, V  Gopalakrishnan, K  Garrett, MR  Joe, B  Citterio, L  Bianchi, G  McBride, M  Dominiczak, A  Adams, DJ  Serikawa, T  Flicek, P  Cuppen, E  Hubner, N  Petretto, E  Gauguier, D  Kwitek, A  Jacob, H  Aitman, TJ 
Citation: Atanur SS, etal., Cell. 2013 Jul 23. pii: S0092-8674(13)00779-4. doi: 10.1016/j.cell.2013.06.040.
Pubmed: (View Article at PubMed) PMID:23890820
DOI: Full-text: DOI:10.1016/j.cell.2013.06.040

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. PAPERCLIP:


Additional Information

RGD Object Information
RGD ID: 7248424
Created: 2013-08-02
Species: All species
Last Modified: 2013-08-02
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.