| Title | Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Baud, 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 Authors | Rat Genome Sequencing and Mapping Consortium |
| Journal | Nat Genet |
| Volume | 45 |
| Issue | 7 |
| Pagination | 767-75 |
| Date Published | 2013 Jul |
| ISSN | 1546-1718 |
| Keywords | Animals, 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. |
| DOI | 10.1038/ng.2644 |
| Alternate Journal | Nat. Genet. |
| PubMed ID | 23708188 |
| PubMed Central ID | PMC3821058 |
| Grant List | 090532/Z/09/Z / / Wellcome Trust / United Kingdom MC_U120061454 / / Medical Research Council / United Kingdom RG/07/005/23633 / / British Heart Foundation / United Kingdom 083573/Z/07/Z / / Wellcome Trust / United Kingdom R01 AR047822 / AR / NIAMS NIH HHS / United States 083573 / / Wellcome Trust / United Kingdom BHFRG/07/005/23633 / / British Heart Foundation / United Kingdom A10976 / / Cancer Research UK / United Kingdom U54 HG003273 / HG / NHGRI NIH HHS / United States G0900084 / / Medical Research Council / United Kingdom 090532 / / Wellcome Trust / United Kingdom 13031 / / Cancer Research UK / United Kingdom 089269/Z/09/Z / / Wellcome Trust / United Kingdom 089269 / / Wellcome Trust / United Kingdom G9900061 / / Medical Research Council / United Kingdom |