A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs
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.
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We thank the hundreds of dog owners who contributed samples; the AKC Canine Health Foundation; S. Hoogstraten-Miller and I. Ginty for assistance at dog shows; P. Cruz for assistance with automated PCR primer designs; S. Kim for analytical assistance, and R. Pelker for assistance with blood serum assays of IGF1. Funded by the National Human Genome Research Institute (E.A.O., N.B.S., E.K., S.D., P.Q., H.G.P., and D.S.M.), the NSF (R.K.W.), NIH grant no. 5T32 HG002536 (M.M.G.), NSF grant 0516310 (C.D.B. and L.Z.), NSF grant DBI 0606461 (B.P.), NIH grant P50 HG002790 (K.Z. and M.N.), and the National Institute of General Medical Sciences 063056, the Judith Chiara Charitable Trust, and the Nestle Purina Company (K.G.L.).
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Published In
Science
Volume 316 | Issue 5821
6 April 2007
6 April 2007
Copyright
American Association for the Advancement of Science.
Submission history
Received: 1 November 2006
Accepted: 8 March 2007
Published in print: 6 April 2007
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www.sciencemag.org/cgi/content/full/316/5821/112/DC1
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Tables S1 to S6
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