title: A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock.
abstract: The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom.
authors.forename: Martina
authors.initials: M
authors.lastname: Johannesson
authors.forename: Regina
authors.initials: R
authors.lastname: Lopez-Aumatell
authors.forename: Pernilla
authors.initials: P
authors.lastname: Stridh
authors.forename: Margarita
authors.initials: M
authors.lastname: Diez
authors.forename: Jonatan
authors.initials: J
authors.lastname: Tuncel
authors.forename: Gloria
authors.initials: G
authors.lastname: Blázquez
authors.forename: Esther
authors.initials: E
authors.lastname: Martinez-Membrives
authors.forename: Toni
authors.initials: T
authors.lastname: Cañete
authors.forename: Elia
authors.initials: E
authors.lastname: Vicens-Costa
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
authors.forename: Richard R
authors.initials: RR
authors.lastname: Copley
authors.forename: Polinka
authors.initials: P
authors.lastname: Hernandez-Pliego
authors.forename: Amennai D
authors.initials: AD
authors.lastname: Beyeen
authors.forename: Johan
authors.initials: J
authors.lastname: Ockinger
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández-Santamaría
authors.forename: Percio S
authors.initials: PS
authors.lastname: Gulko
authors.forename: Max
authors.initials: M
authors.lastname: Brenner
authors.forename: Adolf
authors.initials: A
authors.lastname: Tobeña
authors.forename: Marc
authors.initials: M
authors.lastname: Guitart-Masip
authors.forename: Lydia
authors.initials: L
authors.lastname: Giménez-Llort
authors.forename: Anna
authors.initials: A
authors.lastname: Dominiczak
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: William
authors.initials: W
authors.lastname: Valdar
authors.forename: Eva E
authors.initials: EE
authors.lastname: Redei
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Teruel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains / Q000235:genetics / Q000502:physiology / Q000523:psychology; D001362:Avoidance Learning; D002874:Chromosome Mapping / Q000379:methods*; D005239:Fear; D005260:Female; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats / Q000235:genetics* / Q000502:physiology / Q000523:psychology