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

doi:10.1126/science.1137045

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Science 6 April 2007:
Vol. 316. no. 5821, pp. 112 - 115
DOI: 10.1126/science.1137045

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Reports

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

Nathan B. Sutter,¹ Carlos D. Bustamante,² Kevin Chase,³ Melissa M. Gray,⁴ Keyan Zhao,⁵ Lan Zhu,² Badri Padhukasahasram,² Eric Karlins,¹ Sean Davis,¹ Paul G. Jones,⁶ Pascale Quignon,¹ Gary S. Johnson,⁷ Heidi G. Parker,¹ Neale Fretwell,⁶ Dana S. Mosher,¹ Dennis F. Lawler,⁸ Ebenezer Satyaraj,⁸ Magnus Nordborg,⁵ K. Gordon Lark,³ Robert K. Wayne,⁴ Elaine A. Ostrander¹^*

The domestic dog exhibits greater diversity in body size thanany other terrestrial vertebrate. We used a strategy that exploitsthe breed structure of dogs to investigate the genetic basisof size. First, through a genome-wide scan, we identified amajor quantitative trait locus (QTL) on chromosome 15 influencingsize variation within a single breed. Second, we examined geneticvariation in the 15-megabase interval surrounding the QTL insmall and giant breeds and found marked evidence for a selectivesweep spanning a single gene (IGF1), encoding insulin-like growthfactor 1. A single IGF1 single-nucleotide polymorphism haplotypeis common to all small breeds and nearly absent from giant breeds,suggesting that the same causal sequence variant is a majorcontributor to body size in all small dogs.

¹ National Human Genome Research Institute, Building 50, Room 5349, 50 South Drive MSC 8000, Bethesda, MD 20892–8000, USA.
² Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14850, USA.
³ Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
⁴ Department of Ecology and Environmental Biology, University of California, Los Angeles, CA 90095, USA.
⁵ Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
⁶ The WALTHAM Centre for Pet Nutrition, Waltham on the Wolds, Leicestershire, LE14 4RT, UK.
⁷ Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA.
⁸ Nestle Research Center (NRC-STL), St. Louis, MO 63164, USA.

^* To whom correspondence should be addressed. E-mail: eostrand{at}mail.nih.gov

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