title: 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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Amelie
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authors.forename: Roel
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authors.lastname: Hermsen
authors.forename: Victor
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authors.forename: Delyth
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authors.lastname: Ockinger
authors.forename: Amennai D
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authors.lastname: Gillett
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authors.lastname: Jagodic
authors.forename: Jonatan
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authors.lastname: Tuncel
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authors.lastname: Beattie
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authors.lastname: Huynh
authors.forename: William H
authors.initials: WH
authors.lastname: Miller
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Imranul
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authors.lastname: Alam
authors.forename: Samreen
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authors.lastname: Falak
authors.forename: Mary
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authors.lastname: Osborne-Pellegrin
authors.forename: Esther
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authors.lastname: Martinez-Membrives
authors.forename: Toni
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authors.lastname: Canete
authors.forename: Gloria
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authors.lastname: Blazquez
authors.forename: Elia
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authors.lastname: Vicens-Costa
authors.forename: Carme
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authors.lastname: Mont-Cardona
authors.forename: Sira
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authors.lastname: Diaz-Moran
authors.forename: Adolf
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authors.forename: Oliver
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authors.forename: Diana
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authors.lastname: Zelenika
authors.forename: Kathrin
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authors.forename: Giannino
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authors.lastname: Patone
authors.forename: Anja
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authors.lastname: Bauerfeind
authors.forename: Marie-Therese
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authors.lastname: Bihoreau
authors.forename: Matthias
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authors.lastname: Heinig
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Carola
authors.initials: C
authors.lastname: Rintisch
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authors.initials: H
authors.lastname: Schulz
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authors.initials: DA
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authors.lastname: Worley
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Richard A
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authors.lastname: Gibbs
authors.forename: Mark
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authors.lastname: Lathrop
authors.forename: Nico
authors.initials: N
authors.lastname: Lansu
authors.forename: Pim
authors.initials: P
authors.lastname: Toonen
authors.forename: Frans Paul
authors.initials: FP
authors.lastname: Ruzius
authors.forename: Ewart
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authors.lastname: de Bruijn
authors.forename: Heidi
authors.initials: H
authors.lastname: Hauser
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Thomas
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authors.lastname: Keane
authors.forename: Santosh S
authors.initials: SS
authors.lastname: Atanur
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Aitman
authors.forename: Paul
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authors.lastname: Flicek
authors.forename: Tomas
authors.initials: T
authors.lastname: Malinauskas
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
authors.forename: Diana
authors.initials: D
authors.lastname: Ekman
authors.forename: Regina
authors.initials: R
authors.lastname: Lopez-Aumatell
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: Martina
authors.initials: M
authors.lastname: Johannesson
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernandez-Teruel
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001007:Anxiety / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006331:Heart Diseases / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009103:Multiple Sclerosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D051381:Rats; D017422:Sequence Analysis, DNA / Q000379:methods*