Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

Amelie Baud, Roel Hermsen, Victor Guryev, Pernilla Stridh, Delyth Graham, Martin W. McBride, Tatiana Foroud, Sophie Calderari, Margarita Diez, Johan Ockinger, Amennai D. Beyeen, Alan Gillett, Nada Abdelmagid, Andre Ortlieb Guerreiro-Cacais, Maja Jagodic, Jonatan Tuncel, Ulrika Norin, Elisabeth Beattie, Ngan Huynh, William H. MillerDaniel L. Koller, Imranul Alam, Samreen Falak, Mary Osborne-Pellegrin, Esther Martinez-Membrives, Toni Canete, Gloria Blazquez, Elia Vicens-Costa, Carme Mont-Cardona, Sira Diaz-Moran, Adolf Tobena, Oliver Hummel, Diana Zelenika, Kathrin Saar, Giannino Patone, Anja Bauerfeind, Marie Therese Bihoreau, Matthias Heinig, Young Ae Lee, Carola Rintisch, Herbert Schulz, David A. Wheeler, Kim C. Worley, Donna M. Muzny, Richard A. Gibbs, Mark Lathrop, Nico Lansu, Pim Toonen, Frans Paul Ruzius, Ewart De Bruijn, Heidi Hauser, David J. Adams, Thomas Keane, Santosh S. Atanur, Tim J. Aitman, Paul Flicek, Tomas Malinauskas, E. Yvonne Jones, Diana Ekman, Regina Lopez-Aumatell, Anna F. Dominiczak, Martina Johannesson, Rikard Holmdahl, Tomas Olsson, Dominique Gauguier, Norbert Hubner, Alberto Fernandez-Teruel, Edwin Cuppen, Richard Mott, Jonathan Flint

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102 Scopus citations

Abstract

Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

Original languageEnglish (US)
Pages (from-to)767-775
Number of pages9
JournalNature genetics
Volume45
Issue number7
DOIs
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Genetics

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    Baud, A., Hermsen, R., Guryev, V., Stridh, P., Graham, D., McBride, M. W., Foroud, T., Calderari, S., Diez, M., Ockinger, J., Beyeen, A. D., Gillett, A., Abdelmagid, N., Guerreiro-Cacais, A. O., Jagodic, M., Tuncel, J., Norin, U., Beattie, E., Huynh, N., ... Flint, J. (2013). Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nature genetics, 45(7), 767-775. https://doi.org/10.1038/ng.2644