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Science 316 (5821): 112-115

Copyright © 2007 by the American Association for the Advancement of Science

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*

Abstract: 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.

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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