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


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.

SUBMITTER: Rat Genome Sequencing and Mapping Consortium 

PROVIDER: S-EPMC3821058 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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

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

Nature genetics 20130526 7


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 unexpect  ...[more]

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