Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat
| Autor: | Pamela J. Kaisaki, Edwin Cuppen, Anna Dominiczak, Ana Garcia Diaz, Kathirvel Gopalakrishnan, Paul Flicek, Kathrin Saar, Timothy J. Aitman, Tadao Serikawa, David J. Adams, Georg W. Otto, Laurence Game, Dominique Gauguier, Michael Tschannen, Santosh S. Atanur, Giuseppe Bianchi, Lorena Citterio, Thomas M. Keane, Bina Joe, Oliver Hummel, Enrico Petretto, Anne E. Kwitek, Wei-Wei Chen, Norbert Hubner, Klio Maratou, Howard J. Jacob, Allison B. Sarkis, Victor Guryev, Michael R. Garrett, Man Chun John Ma, Maxime Rotival, Martin W. McBride |
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| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Research Institute for Asthma and COPD (GRIAC), Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2013 |
| Předmět: |
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BB RAT 030204 cardiovascular system & hematology Biology Polymorphism Single Nucleotide Genome General Biochemistry Genetics and Molecular Biology DNA sequencing 03 medical and health sciences 0302 clinical medicine Inbred strain GENETIC-ANALYSIS Phylogenetics Animals OXIDATIVE STRESS CARDIAC-HYPERTROPHY Gene Phylogeny FAWN-HOODED RATS 030304 developmental biology Genetics 0303 health sciences Biochemistry Genetics and Molecular Biology(all) Rats Inbred Strains BLOOD-PRESSURE REGULATION Phenotype Angiotensin II SPONTANEOUSLY HYPERTENSIVE-RAT Rats 3. Good health Disease Models Animal ANGIOTENSIN-II DOMESTICATION Cation transport GENERATION |
| Zdroj: | Atanur, S, Diaz, A G, Maratou, K, Sarkis, A, Rotival, M, Game, L, Tschannen, M, Kaisaki, P, Otto, G, Ma, M C J, Keane, T, Hummel, O, Saar, K, Chen, W, Guryev, V, Gopalakrishnan, K, Garrett, M, Joe, B, Citterio, L, Bianchi, G, Mcbride, M, Dominiczak, A, Adams, D, Serikawa, T, Flicek, P, Cuppen, E, Hubner, N, Petretto, E, Gauguier, D, Kwitek, A, Jacob, H & Aitman, T 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 Cell, 154(3), 691-703. CELL PRESS Cell Cell, 154(3), 691-703. Elsevier B.V. |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2013.06.040 |
| Popis: | Summary 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 Graphical Abstract Highlights • Genomes of 27 rat strains were sequenced; >13 million sequence variants identified • Selective sweeps and coevolved gene clusters were detected in 11 disease models • Previously identified and new disease genes and pathways were identified • This is first evolutionary analysis of artificial selection for disease phenotypes Evolution analysis of artificial selection for disease phenotypes, such as hypertension and diabetes, in 27 rat strains reveals disease-related variants and loci. |
| Databáze: | OpenAIRE |
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