Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse

  1. Jennifer L. Moran1,
  2. Andrew D. Bolton1,
  3. Pamela V. Tran1,
  4. Alison Brown3,
  5. Noelle D. Dwyer4,
  6. Danielle K. Manning1,
  7. Bryan C. Bjork1,
  8. Cheng Li5,
  9. Kate Montgomery3,
  10. Sandra M. Siepka6,
  11. Martha Hotz Vitaterna6,
  12. Joseph S. Takahashi6,7,
  13. Tim Wiltshire8,
  14. David J. Kwiatkowski2,3,
  15. Raju Kucherlapati1,3, and
  16. David R. Beier1,9
  1. 1 Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
  2. 2 Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
  3. 3 Harvard Partners Center for Genetics and Genomics, Harvard Medical School, Cambridge, Massachusetts 02139, USA
  4. 4 Howard Hughes Medical Institute, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
  5. 5 Departments of Biostatistics and Computational Biology, Dana Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02115, USA
  6. 6 Center for Functional Genomics, Northwestern University, Evanston, Illinois 60208, USA
  7. 7 Howard Hughes Medical Institute, Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
  8. 8 Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA

Abstract

Phenotype-driven genetics can be used to create mouse models of human disease and birth defects. However, the utility of these mutant models is limited without identification of the causal gene. To facilitate genetic mapping, we developed a fixed single nucleotide polymorphism (SNP) panel of 394 SNPs as an alternative to analyses using simple sequence length polymorphism (SSLP) marker mapping. With the SNP panel, chromosomal locations for 22 monogenic mutants were identified. The average number of affected progeny genotyped for mapped monogenic mutations is nine. Map locations for several mutants have been obtained with as few as four affected progeny. The average size of genetic intervals obtained for these mutants is 43 Mb, with a range of 17–83 Mb. Thus, our SNP panel allows for identification of moderate resolution map position with small numbers of mice in a high-throughput manner. Importantly, the panel is suitable for mapping crosses from many inbred and wild-derived inbred strain combinations. The chromosomal localizations obtained with the SNP panel allow one to quickly distinguish between potentially novel loci or remutations in known genes, and facilitates fine mapping and positional cloning. By using this approach, we identified DNA sequence changes in two ethylnitrosourea-induced mutants.

Footnotes

  • [Supplemental material is available online at www.genome.org.]

  • Article published online ahead of print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.4563306.

  • ↵9 Corresponding author. E-mail beier{at}receptor.med.harvard.edu; fax (617) 525-4705.

    • Accepted December 6, 2005.
    • Received August 12, 2005.
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  1. Published in Advance February 3, 2006, doi: 10.1101/gr.4563306 Genome Res. 16: 436-440 Cold Spring Harbor Laboratory Press

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