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A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs
Nathan B. Sutter,1Carlos D. Bustamante,2Kevin Chase,3Melissa M. Gray,4Keyan Zhao,5Lan Zhu,2Badri Padhukasahasram,2Eric Karlins,1Sean Davis,1Paul G. Jones,6Pascale Quignon,1Gary S. Johnson,7Heidi G. Parker,1Neale Fretwell,6Dana S. Mosher,1Dennis F. Lawler,8Ebenezer Satyaraj,8Magnus Nordborg,5K. Gordon Lark,3Robert K. Wayne,4Elaine 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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