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Abstract

Single-nucleotide polymorphisms (SNPs) have been the focus of much attention in human genetics because they are extremely abundant and well-suited for automated large-scale genotyping. Human SNPs, however, are less informative than other types of genetic markers (such as simple-sequence length polymorphisms or microsatellites) and thus more loci are required for mapping traits. SNPs offer similar advantages for experimental genetic organisms such as the mouse, but they entail no loss of informativeness because bi-allelic markers are fully informative in analysing crosses between inbred strains. Here we report a large-scale analysis of SNPs in the mouse genome. We characterized the rate of nucleotide polymorphism in eight mouse strains and identified a collection of 2,848 SNPs located in 1,755 sequence-tagged sites (STSs) using high-density oligonucleotide arrays. Three-quarters of these SNPs have been mapped on the mouse genome, providing a first-generation SNP map of the mouse. We have also developed a multiplex genotyping procedure by which a genome scan can be performed with only six genotyping reactions per animal.

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Acknowledgements

We thank H. Nguyen and R. Steen for assistance in RH mapping; the HTS group at Affymetrix Inc. for assistance with chip hybridizations; and J. Singer for providing the backcross DNAs. This research was supported by a research contract from Bristol-Myers Squibb, Millennium Pharmaceuticals Inc. and Affymetrix (E.S.L. and T.J.H.) and the National Institute of Health (HG01806). K.L. is the recipient of a scholarship from the Swedish Institute (4478/1998). J.N.H. is the recipient of a Howard Hughes Medical Institute Postdoctoral Fellowship for Physicians. T.J.H. is a recipient of a Clinician-Scientist award from the Medical Research Council of Canada.

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Affiliations

  1. Whitehead Institute/MIT Center for Genome Research, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

    • Kerstin Lindblad-Toh
    • , Ellen Winchester
    • , Mark J. Daly
    • , David G. Wang
    • , Joel N. Hirschhorn
    • , Jean-Philippe Laviolette
    • , Kristin Ardlie
    • , David E. Reich
    • , Elizabeth Robinson
    • , Pamela Sklar
    • , Thomas J. Hudson
    •  & Eric S. Lander
  2. Bristol-Myers Squibb, P.O. Box 5400, Princeton, New Jersey, USA.

    • David G. Wang
  3. Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA.

    • Joel N. Hirschhorn
  4. Department of Psychiatry, Massachusetts General Hospital , Boston, Massachusetts, USA.

    • Pamela Sklar
  5. Affymetrix, Inc., Santa Clara, California, USA.

    • Nila Shah
    • , Daryl Thomas
    • , Jian-Bing Fan
    • , Thomas Gingeras
    • , Janet Warrington
    •  & Nila Patil
  6. Montreal Genome Centre, McGill University Health Centre, Montréal, Québec, Canada.

    • Thomas J. Hudson
  7. Department of Biology, Massachusetts Institute of Technology , Cambridge, Massachusetts, USA.

    • Eric S. Lander

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Correspondence to Kerstin Lindblad-Toh or Eric S. Lander.

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DOI

https://doi.org/10.1038/74215

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