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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}mail.nih.gov

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.

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

Citation:

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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L. Xu, D. M. Bickhart, J. B. Cole, S. G. Schroeder, J. Song, C. P. V. Tassell, T. S. Sonstegard, and G. E. Liu
Mol Biol Evol 32, 711-725 (1 March 2015)

Feather Development Genes and Associated Regulatory Innovation Predate the Origin of Dinosauria
C. B. Lowe, J. A. Clarke, A. J. Baker, D. Haussler, and S. V. Edwards
Mol Biol Evol 32, 23-28 (1 January 2015)

Genetic Determinants for Enzymatic Digestion of Lignocellulosic Biomass Are Independent of Those for Lignin Abundance in a Maize Recombinant Inbred Population
B. W. Penning, R. W. Sykes, N. C. Babcock, C. K. Dugard, M. A. Held, J. F. Klimek, J. T. Shreve, M. Fowler, A. Ziebell, M. F. Davis et al.
Plant Physiol. 165, 1475-1487 (1 August 2014)

Genomic basis for the convergent evolution of electric organs
J. R. Gallant, L. L. Traeger, J. D. Volkening, H. Moffett, P.-H. Chen, C. D. Novina, G. N. Phillips, R. Anand, G. B. Wells, M. Pinch et al.
Science 344, 1522-1525 (27 June 2014)

Establishing the validity of domestication genes using DNA from ancient chickens
L. Girdland Flink, R. Allen, R. Barnett, H. Malmstrom, J. Peters, J. Eriksson, L. Andersson, K. Dobney, and G. Larson
Proc. Natl. Acad. Sci. USA 111, 6184-6189 (29 April 2014)

Insulin signalling underlies both plasticity and divergence of a reproductive trait in Drosophila
D. A. Green, and C. G. Extavour
Proc R Soc B 281, 20132673-20132673 (22 March 2014)

Evolutionary genetics and implications of small size and twinning in callitrichine primates
R. A. Harris, S. D. Tardif, T. Vinar, D. E. Wildman, J. N. Rutherford, J. Rogers, K. C. Worley, and K. M. Aagaard
Proc. Natl. Acad. Sci. USA 111, 1467-1472 (28 January 2014)

Transmissible Dog Cancer Genome Reveals the Origin and History of an Ancient Cell Lineage
E. P. Murchison, D. C. Wedge, L. B. Alexandrov, B. Fu, I. Martincorena, Z. Ning, J. M. C. Tubio, E. I. Werner, J. Allen, A. B. De Nardi et al.
Science 343, 437-440 (24 January 2014)

Dynamics of Adaptive Alleles in Divergently Selected Body Weight Lines of Chickens
M. E. Pettersson, A. M. Johansson, P. B. Siegel, and O. Carlborg
G3 3, 2305-2312 (9 December 2013)

Derived variants at six genes explain nearly half of size reduction in dog breeds
M. Rimbault, H. C. Beale, J. J. Schoenebeck, B. C. Hoopes, J. J. Allen, P. Kilroy-Glynn, R. K. Wayne, N. B. Sutter, and E. A. Ostrander
Genome Res 23, 1985-1995 (1 December 2013)

Six Classroom Exercises to Teach Natural Selection to Undergraduate Biology Students
S. T. Kalinowski, M. J. Leonard, T. M. Andrews, and A. R. Litt
cellbioed 12, 483-493 (1 September 2013)

The 2013 Genetics Society of America Medal: Elaine A. Ostrander
J. Schimenti, and M. Halpern
Genetics 194, 5-7 (1 May 2013)

Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity
A. Bartke, L. Y. Sun, and V. Longo
Physiol. Rev. 93, 571-598 (1 April 2013)

Genomic Diversity and Evolution of the Head Crest in the Rock Pigeon
M. D. Shapiro, Z. Kronenberg, C. Li, E. T. Domyan, H. Pan, M. Campbell, H. Tan, C. D. Huff, H. Hu, A. I. Vickrey et al.
Science 339, 1063-1067 (1 March 2013)

Differences in Selection Drive Olfactory Receptor Genes in Different Directions in Dogs and Wolf
R. Chen, D. M. Irwin, and Y.-P. Zhang
Mol Biol Evol 29, 3475-3484 (1 November 2012)

So many doggone traits: mapping genetics of multiple phenotypes in the domestic dog
M. Rimbault, and E. A. Ostrander
Hum Mol Genet 21, R52-R57 (15 October 2012)

Growth Factors, Nutrient Signaling, and Cardiovascular Aging
L. Fontana, M. Vinciguerra, and V. D. Longo
Circ. Res. 110, 1139-1150 (13 April 2012)

Quiescence: early evolutionary origins and universality do not imply uniformity
P. H. O'Farrell, M. Vinciguerra, and V. D. Longo
Phil Trans R Soc B 366, 3498-3507 (27 December 2011)

Heterozygote advantage as a natural consequence of adaptation in diploids
D. Sellis, B. J. Callahan, D. A. Petrov, and P. W. Messer
Proc. Natl. Acad. Sci. USA 108, 20666-20671 (20 December 2011)

Deciphering the genetic basis of animal domestication
P. Wiener, and S. Wilkinson
Proc R Soc B 278, 3161-3170 (7 November 2011)

Mechanisms and pathways of growth failure in primordial dwarfism
A. Klingseisen, and A. P. Jackson
Genes Dev. 25, 2011-2024 (1 October 2011)

Carnivore-Specific SINEs (Can-SINEs): Distribution, Evolution, and Genomic Impact
K. B. Walters-Conte, D. L. E. Johnson, M. W. Allard, and J. Pecon-Slattery
J Hered 102, S2-S10 (1 September 2011)

The Genetic Structure of Domestic Rabbits
M. Carneiro, S. Afonso, A. Geraldes, H. Garreau, G. Bolet, S. Boucher, A. Tircazes, G. Queney, M. W. Nachman, N. Ferrand et al.
Mol Biol Evol 28, 1801-1816 (1 June 2011)

Cutaneous MCTs: Associations with Spay/Neuter Status, Breed, Body Size, and Phylogenetic Cluster
C. R. White, A. E. Hohenhaus, J. Kelsey, and E. Procter-Gray
Journal of the American Animal Hospital Association 47, 210-216 (1 May 2011)

Intraspecies disparity in growth rate is associated with differences in expression of local growth plate regulators
M. A. Tryfonidou, H. A. W. Hazewinkel, F. M. Riemers, B. Brinkhof, L. C. Penning, and M. Karperien
Am. J. Physiol. Endocrinol. Metab. 299, E1044-E1052 (1 December 2010)

Small Is Beautiful: Insulin-Like Growth Factors and Their Role in Growth, Development, and Cancer
R. G. Maki, H. A. W. Hazewinkel, F. M. Riemers, B. Brinkhof, L. C. Penning, and M. Karperien
JCO 28, 4985-4995 (20 November 2010)

Genetic architecture of a feeding adaptation: garter snake (Thamnophis) resistance to tetrodotoxin bearing prey
C. R. Feldman, E. D. Brodie, E. D. Brodie, and M. E. Pfrender
Proc R Soc B 277, 3317-3325 (7 November 2010)

Whole-Genome Positive Selection and Habitat-Driven Evolution in a Shallow and a Deep-Sea Urchin
T. A. Oliver, D. A. Garfield, M. K. Manier, R. Haygood, G. A. Wray, and S. R. Palumbi
Genome Biol Evol 2, 800-814 (1 November 2010)

Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth
J. C. Lui, P. Forcinito, M. Chang, W. Chen, K. M. Barnes, and J. Baron
FASEB J. 24, 3083-3092 (1 August 2010)

The role of insulin/IGF-like signaling in C. elegans longevity and aging
R. Kaletsky, and C. T. Murphy
DMM 3, 415-419 (1 July 2010)

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K. Reynaud, S. Chastant-Maillard, S. Batard, S. Thoumire, and P. Monget
J Endocrinol 206, 85-92 (1 July 2010)

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J. F. Innes, and P. Clegg
Rheumatology (Oxford) 49, 1030-1039 (1 June 2010)

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S. T. Kalinowski, M. J. Leonard, and T. M. Andrews
cellbioed 9, 87-97 (1 June 2010)

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H. P. Xu, X. Shen, M. Zhou, C. L. Luo, L. Kang, Y. Liang, H. Zeng, Q. H. Nie, D. X. Zhang, X. Q. Zhang et al.
Poultry Science 89, 428-438 (1 March 2010)

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J. M. Akey, A. L. Ruhe, D. T. Akey, A. K. Wong, C. F. Connelly, J. Madeoy, T. J. Nicholas, and M. W. Neff
Proc. Natl. Acad. Sci. USA 107, 1160-1165 (19 January 2010)

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E. Cadieu, M. W. Neff, P. Quignon, K. Walsh, K. Chase, H. G. Parker, B. M. VonHoldt, A. Rhue, A. Boyko, A. Byers et al.
Science 326, 150-153 (2 October 2009)

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R. J. Denver, P. M. Hopkins, S. D. McCormick, C. R. Propper, L. Riddiford, S. A. Sower, and J. C. Wingfield
Integr. Comp. Biol. 49, 339-348 (1 October 2009)

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A. P. Bhole, B. P. Flynn, M. Liles, N. Saeidi, C. A. Dimarzio, and J. W. Ruberti
Phil Trans R Soc A 367, 3339-3362 (13 September 2009)

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P. Quignon, J.J. Schoenebeck, K. Chase, H.G. Parker, D.S. Mosher, G.S. Johnson, K.G. Lark, and E.A. Ostrander
Cold Spring Harb Symp Quant Biol 0, sqb.2009.74.009v1-sqb.2009.74.009 (28 August 2009)

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Science 325, 958-959 (21 August 2009)

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Science 325, 995-998 (21 August 2009)

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K. Chase, P. Jones, A. Martin, E. A. Ostrander, and K. G. Lark
J Hered 100, S37-S41 (1 July 2009)

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R. H. Devlin, D. Sakhrani, W. E. Tymchuk, M. L. Rise, and B. Goh
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T. J. Nicholas, Z. Cheng, M. Ventura, K. Mealey, E. E. Eichler, and J. M. Akey
Genome Res 19, 491-499 (1 March 2009)

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W.-K. Chen, J. D. Swartz, L. J. Rush, and C. E. Alvarez
Genome Res 19, 500-509 (1 March 2009)

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S. Frazier-Bowers, R. Rincon-Rodriguez, J. Zhou, K. Alexander, and E. Lange
JDR 88, 56-60 (1 January 2009)

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F. Cruz, C. Vila, and M. T. Webster
Mol Biol Evol 25, 2331-2336 (1 November 2008)

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M. E Picha, M. J Turano, C. K Tipsmark, and R. J Borski
J Endocrinol 199, 81-94 (1 October 2008)

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C. J. Schneider, M. J Turano, C. K Tipsmark, and R. J Borski
Integr. Comp. Biol. 48, 520-526 (1 October 2008)

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P. Jones, K. Chase, A. Martin, P. Davern, E. A. Ostrander, and K. G. Lark
Genetics 179, 1033-1044 (1 June 2008)

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Y. Suh, G. Atzmon, M.-O. Cho, D. Hwang, B. Liu, D. J. Leahy, N. Barzilai, and P. Cohen
Proc. Natl. Acad. Sci. USA 105, 3438-3442 (4 March 2008)

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T. Takada, A. Mita, A. Maeno, T. Sakai, H. Shitara, Y. Kikkawa, K. Moriwaki, H. Yonekawa, and T. Shiroishi
Genome Res 18, 500-508 (1 March 2008)

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H. S. Makinen, T. Shikano, J. M. Cano, and J. Merila
Genetics 178, 453-465 (1 January 2008)

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P. Mazur, S.P Leibo, and G. E Seidel
Biol. Reprod. 78, 2-12 (1 January 2008)

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I. Pilecka, C. Patrignani, R. Pescini, M.-L. Curchod, D. Perrin, Y. Xue, J. Yasenchak, A. Clark, M. C. Magnone, P. Zaratin et al.
J Biol Chem 282, 35405-35415 (30 November 2007)

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M. C. Flannery, C. Patrignani, R. Pescini, M.-L. Curchod, D. Perrin, Y. Xue, J. Yasenchak, A. Clark, M. C. Magnone, P. Zaratin et al.
AM BIOL TEACH 69, 422-425 (1 September 2007)

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J. Laidlaw, Y. Gelfand, K.-W. Ng, H. R. Garner, R. Ranganathan, G. Benson, and J. W. Fondon
J Hered 0, esm017v2-20 (3 August 2007)

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E. A. Ostrander, Y. Gelfand, K.-W. Ng, H. R. Garner, R. Ranganathan, G. Benson, and J. W. Fondon
Science 317, 45-45 (6 July 2007)

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Br J Ophthalmol 91, 988-988 (1 July 2007)

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