High-resolution mapping of quantitative trait loci in outbred mice (original) (raw)

Nature Genetics volume 21, pages 305–308 (1999)Cite this article

Abstract

Screening the whole genome of a cross between two inbred animal strains has proved to be a powerful method for detecting genetic loci underlying quantitative behavioural traits1,2,3,4,5,6,7, but the level of resolution offered by quantitative trait loci (QTL) mapping is still too coarse to permit molecular cloning of the genetic determinants8. To achieve high-resolution mapping, we used an outbred stock of mice for which the entire genealogy is known. The heterogeneous stock (HS) was established 30 years ago from an eight-way cross of C57BL/6, BALB/c, RIII, AKR, DBA/2, I, A/J and C3H inbred mouse strains9. At the time of the experiment reported here, the HS mice were at generation 58, theoretically offering at least a 30-fold increase in resolution for QTL mapping compared with a backcross or an F2 intercross10,11. Using the HS mice we have mapped a QTL influencing a psychological trait in mice to a 0.8-cM interval on chromosome 1. This method allows simultaneous fine mapping of multiple QTLs, as shown by our report of a second QTL on chromosome 12. The high resolution possible with this approach makes QTLs accessible to positional cloning.

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Acknowledgements

We thank A. Darvasi and L. Cardon for help with the analyses, J. DeFries for comments on the manuscript and S. Brown and the MRC Mammalian Genetics Unit at Harwell, Oxfordshire for help. This work was supported by the Wellcome Trust (C.J.T., A.N. and J.F.).

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Authors and Affiliations

  1. Institute of Molecular Medicine, John Radcliffe Hospital , Oxford, OX3 9DS, UK
    Christopher J. Talbot, Alison Nicod & Jonathan Flint
  2. Institute for Behavioral Genetics, University of Colorado , Boulder, 80309, Colorado, USA
    Stacey S. Cherny, David W. Fulker & Allan C. Collins
  3. Social, Genetic and Developmental and Psychiatric Research Centre, Instititute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
    Stacey S. Cherny & David W. Fulker

Authors

  1. Christopher J. Talbot
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  2. Alison Nicod
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  3. Stacey S. Cherny
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  4. David W. Fulker
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  5. Allan C. Collins
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  6. Jonathan Flint
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Correspondence toJonathan Flint.

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Talbot, C., Nicod, A., Cherny, S. et al. High-resolution mapping of quantitative trait loci in outbred mice.Nat Genet 21, 305–308 (1999). https://doi.org/10.1038/6825

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