A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: The NIH heterogeneous stock
- Martina Johannesson1,
- Regina Lopez-Aumatell2,
- Margarita Diez3,
- Jonatan Tuncel4,
- Gloria Blazquez2,
- Esther Martinez2,
- Antoni Canete2,
- Elia Vicens-Costa2,
- Delyth Graham5,
- Richard Copley1,
- Polinka Hernandez-Pliego1,
- Amennai Beyeen3,
- Pernilla Stridh6,
- Johan Ockinger3,
- Cristina Fernandez1,
- Percio S. Gulko7,
- Max Brenner7,
- Adolf Tobena2,
- Marc Guitart-Masip2,
- Lydia Gimenez-Llort2,
- Anna Dominiczak5,
- Rikard Holmdahl8,
- Dominique Gauguier1,
- Tomas Olsson3,
- Richard Mott1,
- William Valdar1,
- Eva Redei9,
- Alberto Fernandez-Teruel2, and
- Jonathan Flint1,10
- 1 Wellcome Trust Centre for Human Genetics;
- 2 Autonomous University of Barcelona;
- 3 Karolinska University Hospital;
- 4 Karolinska University Hospita;
- 5 University of Glasgow;
- 6 Karolinska University Hospital,;
- 7 The Feinstein Institute for Medical Research;
- 8 Karolinska Institutet;
- 9 Northwestern University
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. Using 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.
Footnotes
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- Received May 29, 2008.
- Accepted October 16, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
