A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock.
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.
Johannesson
Martina
M
Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom.
Lopez-Aumatell
Regina
R
Stridh
Pernilla
P
Diez
Margarita
M
Tuncel
Jonatan
J
Blázquez
Gloria
G
Martinez-Membrives
Esther
E
Cañete
Toni
T
Vicens-Costa
Elia
E
Graham
Delyth
D
Copley
Richard R
RR
Hernandez-Pliego
Polinka
P
Beyeen
Amennai D
AD
Ockinger
Johan
J
Fernández-Santamaría
Cristina
C
Gulko
Percio S
PS
Brenner
Max
M
Tobeña
Adolf
A
Guitart-Masip
Marc
M
Giménez-Llort
Lydia
L
Dominiczak
Anna
A
Holmdahl
Rikard
R
Gauguier
Dominique
D
Olsson
Tomas
T
Mott
Richard
R
Valdar
William
W
Redei
Eva E
EE
Fernández-Teruel
Alberto
A
Flint
Jonathan
J
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