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

TitleCombined sequence-based and genetic mapping analysis of complex traits in outbred rats.
Publication TypeJournal Article
Year of Publication2013
AuthorsBaud, A, Hermsen, R, Guryev, V, Stridh, P, Graham, D, McBride, MW, Foroud, T, Calderari, S, Diez, M, Ockinger, J, Beyeen, AD, Gillett, A, Abdelmagid, N, Guerreiro-Cacais, AOrtlieb, Jagodic, M, Tuncel, J, Norin, U, Beattie, E, Huynh, N, Miller, WH, Koller, DL, Alam, I, Falak, S, Osborne-Pellegrin, M, Martinez-Membrives, E, Canete, T, Blazquez, G, Vicens-Costa, E, Mont-Cardona, C, Diaz-Moran, S, Tobena, A, Hummel, O, Zelenika, D, Saar, K, Patone, G, Bauerfeind, A, Bihoreau, M-T, Heinig, M, Lee, Y-A, Rintisch, C, Schulz, H, Wheeler, DA, Worley, KC, Muzny, DM, Gibbs, RA, Lathrop, M, Lansu, N, Toonen, P, Ruzius, FPaul, de Bruijn, E, Hauser, H, Adams, DJ, Keane, T, Atanur, SS, Aitman, TJ, Flicek, P, Malinauskas, T, E Jones, Y, Ekman, D, Lopez-Aumatell, R, Dominiczak, AF, Johannesson, M, Holmdahl, R, Olsson, T, Gauguier, D, Hübner, N, Fernandez-Teruel, A, Cuppen, E, Mott, R, Flint, J
Corporate AuthorsRat Genome Sequencing and Mapping Consortium
JournalNat Genet
Volume45
Issue7
Pagination767-75
Date Published2013 Jul
ISSN1546-1718
KeywordsAnimals, Animals, Outbred Strains, Anxiety, Chromosome Mapping, Genetic Variation, Genotype, Heart Diseases, Humans, Mice, Mice, Inbred C57BL, Models, Molecular, Multiple Sclerosis, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Rats, Sequence Analysis, DNA
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.
DOI10.1038/ng.2644
Alternate JournalNat Genet
PubMed ID23708188
PubMed Central IDPMC3821058
Grant List089269/Z/09/Z / WT_ / Wellcome Trust / United Kingdom
A10976 / CRUK_ / Cancer Research UK / United Kingdom
BHFRG/07/005/23633 / BHF_ / British Heart Foundation / United Kingdom
U54 HG003273 / HG / NHGRI NIH HHS / United States
MC_U120061454 / MRC_ / Medical Research Council / United Kingdom
G0900084 / MRC_ / Medical Research Council / United Kingdom
090532 / WT_ / Wellcome Trust / United Kingdom
/ WT_ / Wellcome Trust / United Kingdom
G9900061 / MRC_ / Medical Research Council / United Kingdom
083573/Z/07/Z / WT_ / Wellcome Trust / United Kingdom
R01 AR047822 / AR / NIAMS NIH HHS / United States
083573 / WT_ / Wellcome Trust / United Kingdom
089269 / WT_ / Wellcome Trust / United Kingdom
090532/Z/09/Z / WT_ / Wellcome Trust / United Kingdom
RG/07/005/23633 / BHF_ / British Heart Foundation / United Kingdom
13031 / CRUK_ / Cancer Research UK / United Kingdom

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