A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: The NIH heterogeneous stock

  1. Martina Johannesson1,
  2. Regina Lopez-Aumatell2,
  3. Pernilla Stridh3,
  4. Margarita Diez3,
  5. Jonatan Tuncel4,
  6. Gloria Blázquez2,
  7. Esther Martinez-Membrives2,
  8. Toni Cañete2,
  9. Elia Vicens-Costa2,
  10. Delyth Graham5,
  11. Richard R. Copley1,
  12. Polinka Hernandez-Pliego1,
  13. Amennai D. Beyeen3,
  14. Johan Öckinger3,
  15. Cristina Fernández-Santamaría1,
  16. Percio S. Gulko6,
  17. Max Brenner6,
  18. Adolf Tobeña2,
  19. Marc Guitart-Masip2,
  20. Lydia Giménez-Llort2,
  21. Anna Dominiczak5,
  22. Rikard Holmdahl4,
  23. Dominique Gauguier1,
  24. Tomas Olsson3,
  25. Richard Mott1,
  26. William Valdar1,
  27. Eva E. Redei7,
  28. Alberto Fernández-Teruel2 and
  29. Jonathan Flint1,8
  1. 1 Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom;
  2. 2 Medical Psychology Unit, Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, School of Medicine, Autonomous University of Barcelona, 08193-Bellaterra, Barcelona, Spain;
  3. 3 Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet CMM, Karolinska University Hospital, 171 76 Stockholm, Sweden;
  4. 4 Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;
  5. 5 BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow G12 8TA, United Kingdom;
  6. 6 Laboratory of Experimental Rheumatology, Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA;
  7. 7 Northwestern University Feinberg School of Medicine, The Asher Center, Department of Psychiatry and Behavioral Sciences, Chicago, Illinois 60611, USA

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.

Footnotes

  • ↵8 Corresponding author.

    ↵E-mail jf{at}well.ox.ac.uk; fax 44-1865-287501.

  • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.081497.108.

    • Received May 29, 2008.
    • Accepted October 16, 2008.
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  1. Published in Advance October 29, 2008, doi: 10.1101/gr.081497.108 Genome Res. 19: 150-158 Copyright © 2009, Cold Spring Harbor Laboratory Press

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