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A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs

Science, 6 April 2007
Vol. 316, Issue 5821, p. 112-115
DOI: 10.1126/science.1137045

A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs

  1. Nathan B. Sutter1,
  2. Carlos D. Bustamante2,
  3. Kevin Chase3,
  4. Melissa M. Gray4,
  5. Keyan Zhao5,
  6. Lan Zhu2,
  7. Badri Padhukasahasram2,
  8. Eric Karlins1,
  9. Sean Davis1,
  10. Paul G. Jones6,
  11. Pascale Quignon1,
  12. Gary S. Johnson7,
  13. Heidi G. Parker1,
  14. Neale Fretwell6,
  15. Dana S. Mosher1,
  16. Dennis F. Lawler8,
  17. Ebenezer Satyaraj8,
  18. Magnus Nordborg5,
  19. K. Gordon Lark3,
  20. Robert K. Wayne4,
  21. Elaine A. Ostrander1,*
  1. 1 National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892–8000, USA.
  2. 2 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14850, USA.
  3. 3 Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
  4. 4 Department of Ecology and Environmental Biology, University of California, Los Angeles, CA 90095, USA.
  5. 5 Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
  6. 6 The WALTHAM Centre for Pet Nutrition, Waltham on the Wolds, Leicestershire, LE14 4RT, UK.
  7. 7 Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
  8. 8 Nestle Research Center (NRC-STL), St. Louis, MO 63164, USA.
  1. * To whom correspondence should be addressed. E-mail: eostrand{at}


The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.

  • Received for publication 1 November 2006.
  • Accepted for publication 8 March 2007.


N. B. Sutter, C. D. Bustamante, K. Chase, M. M. Gray, K. Zhao, L. Zhu, B. Padhukasahasram, E. Karlins, S. Davis, P. G. Jones, P. Quignon, G. S. Johnson, H. G. Parker, N. Fretwell, D. S. Mosher, D. F. Lawler, E. Satyaraj, M. Nordborg, K. G. Lark, R. K. Wayne, and E. A. Ostrander, A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Science 316, 112-115 (2007).

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