A Simple Genetic Architecture Underlies Morphological Variation in Dogs
Adam R. Boyko1,2#, Pascale Quignon3#, Lin Li2#, Jeffrey J. Schoenebeck3, Jeremiah D. Degenhardt2, Kirk E. Lohmueller2, Keyan Zhao1,2, Abra Brisbin2, Heidi G. Parker3, Bridgett M. vonHoldt4, Michele Cargill5, Adam Auton2, Andy Reynolds2, Abdel G. Elkahloun3, Marta Castelhano6, Dana S. Mosher3, Nathan B. Sutter2,6, Gary S. Johnson7, John Novembre4, Melissa J. Hubisz2, Adam Siepel2, Robert K. Wayne4, Carlos D. Bustamante1,2¶*,Elaine A. Ostrander3¶*
1 Department of Genetics, Stanford School of Medicine, Stanford, California, United States of America, 2 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America, 3 Cancer Genetic Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 4 Department of Ecology and Environmental Biology, University of California, Los Angeles, California, United States of America, 5 Affymetrix Corporation, Santa Clara, California, United States of America, 6 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America, 7Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri, United States of America
Abstract
Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.
Author Summary
Dogs offer a unique system for the study of genes controlling morphology. DNA from 915 dogs from 80 domestic breeds, as well as a set of feral dogs, was tested at over 60,000 points of variation and the dataset analyzed using novel methods to find loci regulating body size, head shape, leg length, ear position, and a host of other traits. Because each dog breed has undergone strong selection by breeders to have a particular appearance, there is a strong footprint of selection in regions of the genome that are important for controlling traits that define each breed. These analyses identified new regions of the genome, or loci, that are important in controlling body size and shape. Our results, which feature the largest number of domestic dogs studied at such a high level of genetic detail, demonstrate the power of the dog as a model for finding genes that control the body plan of mammals. Further, we show that the remarkable diversity of form in the dog, in contrast to some other species studied to date, appears to have a simple genetic basis dominated by genes of major effect.
Citation: Boyko AR, Quignon P, Li L, Schoenebeck JJ, Degenhardt JD, et al. (2010) A Simple Genetic Architecture Underlies Morphological Variation in Dogs. PLoS Biol 8(8): e1000451. doi:10.1371/journal.pbio.1000451
Academic Editor: Hopi E. Hoekstra, Harvard University, United States of America
Received: January 25, 2010; Accepted: July 2, 2010; Published: August 10, 2010
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: We acknowledge grants NIH/NHLBI 1U01HL084706, NSF (DBI) 0516310, NSF (DBI) 0701382, NSF (DEB) 0948510, the Cornell Center for Vertebrate Genomics, and the Intramural Program of the National Human Genome Research Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AKC, American Kennel Club; BMI, body mass index; LD, linkage disequilibrium; MAF, minor allele frequency; QTL, Quantitative Trait Loci
* E-mail: cdbustam@stanford.edu (CDB); eostrand@mail.nih.gov (EAO)
# These authors contributed equally to this work.
¶ These authors co-directed the work.
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