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

Santosh S. Atanur; Ana Garcia Diaz; Klio Maratou; Allison Sarkis; Maxime Rotival; Laurence Game; Michael R. Tschannen; Pamela J. Kaisaki; Georg W. Otto; Man Chun John Ma; Thomas M. Keane; Oliver Hummel; Kathrin Saar; Wei Chen; Victor Guryev; Kathirvel Gopalakrishnan; Michael R. Garrett; Bina Joe; Lorena Citterio; Giuseppe Bianchi; Martin McBride; Anna Dominiczak; David J. Adams; Tadao Serikawa; Paul Flicek; Edwin Cuppen; Norbert Hubner; Enrico Petretto; Dominique Gauguier; Anne Kwitek; Howard Jacob; Timothy J. Aitman

doi:10.1016/j.cell.2013.06.040

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

Santosh S. Atanur, Ana Garcia Diaz, Klio Maratou, Allison Sarkis, Maxime Rotival, Laurence Game, Michael R. Tschannen, Pamela J. Kaisaki, Georg W. Otto, Man Chun John Ma, Thomas M. Keane, Oliver Hummel, Kathrin Saar, Wei Chen, Victor Guryev, Kathirvel Gopalakrishnan, Michael R. Garrett, Bina Joe, Lorena Citterio, Giuseppe BianchiMartin McBride, Anna Dominiczak, David J. Adams, Tadao Serikawa, Paul Flicek, Edwin Cuppen, Norbert Hubner, Enrico Petretto, Dominique Gauguier, Anne Kwitek, Howard Jacob, Timothy J. Aitman

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article › peer-review

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. PaperClip

Original language	English
Pages (from-to)	691-703
Number of pages	13
Journal	Cell
Volume	154
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2013.06.040
Publication status	Published - Aug 1 2013

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2013.06.040

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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., ... Aitman, T. J. (2013). Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. Cell, 154(3), 691-703. https://doi.org/10.1016/j.cell.2013.06.040

Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. / Atanur, Santosh S.; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R.; Kaisaki, Pamela J.; Otto, Georg W.; Ma, Man Chun John; Keane, Thomas M.; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R.; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J.; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J.

In: Cell, Vol. 154, No. 3, 01.08.2013, p. 691-703.

Research output: Contribution to journal › Article › peer-review

Atanur, SS, Diaz, AG, Maratou, K, Sarkis, A, Rotival, M, Game, L, Tschannen, MR, Kaisaki, PJ, Otto, GW, Ma, MCJ, 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 2013, 'Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat', Cell, vol. 154, no. 3, pp. 691-703. https://doi.org/10.1016/j.cell.2013.06.040

Atanur, Santosh S. ; Diaz, Ana Garcia ; Maratou, Klio ; Sarkis, Allison ; Rotival, Maxime ; Game, Laurence ; Tschannen, Michael R. ; Kaisaki, Pamela J. ; Otto, Georg W. ; Ma, Man Chun John ; Keane, Thomas M. ; Hummel, Oliver ; Saar, Kathrin ; Chen, Wei ; Guryev, Victor ; Gopalakrishnan, Kathirvel ; Garrett, Michael R. ; Joe, Bina ; Citterio, Lorena ; Bianchi, Giuseppe ; McBride, Martin ; Dominiczak, Anna ; Adams, David J. ; Serikawa, Tadao ; Flicek, Paul ; Cuppen, Edwin ; Hubner, Norbert ; Petretto, Enrico ; Gauguier, Dominique ; Kwitek, Anne ; Jacob, Howard ; Aitman, Timothy J. / Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. In: Cell. 2013 ; Vol. 154, No. 3. pp. 691-703.

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AU - Atanur, Santosh S.

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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.

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AU - Chen, Wei

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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.

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