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

Atanur, S.S. et al. (2013) Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. Cell, 154(3), pp. 691-703. (doi:10.1016/j.cell.2013.06.040)

[img]
Preview
Text
84078.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McBride, Dr Martin and Dominiczak, Professor Anna
Authors: Atanur, S.S., Diaz, A.G., Maratou, K., Sarkis, A., Rotival, M., Game, L., Tschannen, M.R., Kaisaki, P.J., Otto, G.W., Ma, M.C.J., Keane, T.M., Hummel, O., Saar, K., Chen, W., Guryev, V., Gopalakrishnan, K., Garrett, M.R., Joe, B., Citterio, L., Bianchi, G., McBride, M., Dominiczak, A., Adams, D.J., Serikawa, T., Flicek, P., Cuppen, E., Hubner, N., Petretto, E., Gauguier, D., Kwitek, A., Jacob, H., and Aitman, T.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Cell
Publisher:Cell Press
ISSN:0092-8674
ISSN (Online):1097-4172
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Cell 154(3):691-703
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record