TY - JOUR
T1 - Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat
AU - Atanur, Santosh S.
AU - Diaz, Ana Garcia
AU - Maratou, Klio
AU - Sarkis, Allison
AU - Rotival, Maxime
AU - Game, Laurence
AU - Tschannen, Michael R.
AU - Kaisaki, Pamela J.
AU - Otto, Georg W.
AU - Ma, Man Chun John
AU - Keane, Thomas M.
AU - Hummel, Oliver
AU - Saar, Kathrin
AU - Chen, Wei
AU - Guryev, Victor
AU - Gopalakrishnan, Kathirvel
AU - Garrett, Michael R.
AU - Joe, Bina
AU - Citterio, Lorena
AU - Bianchi, Giuseppe
AU - McBride, Martin
AU - Dominiczak, Anna
AU - Adams, David J.
AU - Serikawa, Tadao
AU - Flicek, Paul
AU - Cuppen, Edwin
AU - Hubner, Norbert
AU - Petretto, Enrico
AU - Gauguier, Dominique
AU - Kwitek, Anne
AU - Jacob, Howard
AU - Aitman, Timothy J.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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
AB - 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
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U2 - 10.1016/j.cell.2013.06.040
DO - 10.1016/j.cell.2013.06.040
M3 - Article
C2 - 23890820
AN - SCOPUS:84881176167
VL - 154
SP - 691
EP - 703
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -