Article

Nature 438, 803-819 (8 December 2005) | doi:10.1038/nature04338; Received 9 August 2005; Accepted 11 October 2005

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Kerstin Lindblad-Toh1, Claire M Wade1,2, Tarjei S. Mikkelsen1,3, Elinor K. Karlsson1,4, David B. Jaffe1, Michael Kamal1, Michele Clamp1, Jean L. Chang1, Edward J. Kulbokas, III1, Michael C. Zody1, Evan Mauceli1, Xiaohui Xie1, Matthew Breen5, Robert K. Wayne6, Elaine A. Ostrander7, Chris P. Ponting8, Francis Galibert9, Douglas R. Smith10, Pieter J. deJong11, Ewen Kirkness12, Pablo Alvarez1, Tara Biagi1, William Brockman1, Jonathan Butler1, Chee-Wye Chin1, April Cook1, James Cuff1, Mark J. Daly1,2, David DeCaprio1, Sante Gnerre1, Manfred Grabherr1, Manolis Kellis1,13, Michael Kleber1, Carolyne Bardeleben6, Leo Goodstadt8, Andreas Heger8, Christophe Hitte9, Lisa Kim7, Klaus-Peter Koepfli6, Heidi G. Parker7, John P. Pollinger6, Stephen M. J. Searle14, Nathan B. Sutter7, Rachael Thomas5, Caleb Webber8, Jennifer Baldwin16, Adal Abebe16, Amr Abouelleil16, Lynne Aftuck16, Mostafa Ait-zahra16, Tyler Aldredge16, Nicole Allen16, Peter An16, Scott Anderson16, Claudel Antoine16, Harindra Arachchi16, Ali Aslam16, Laura Ayotte16, Pasang Bachantsang16, Andrew Barry16, Tashi Bayul16, Mostafa Benamara16, Aaron Berlin16, Daniel Bessette16, Berta Blitshteyn16, Toby Bloom16, Jason Blye16, Leonid Boguslavskiy16, Claude Bonnet16, Boris Boukhgalter16, Adam Brown16, Patrick Cahill16, Nadia Calixte16, Jody Camarata16, Yama Cheshatsang16, Jeffrey Chu16, Mieke Citroen16, Alville Collymore16, Patrick Cooke16, Tenzin Dawoe16, Riza Daza16, Karin Decktor16, Stuart DeGray16, Norbu Dhargay16, Kimberly Dooley16, Kathleen Dooley16, Passang Dorje16, Kunsang Dorjee16, Lester Dorris16, Noah Duffey16, Alan Dupes16, Osebhajajeme Egbiremolen16, Richard Elong16, Jill Falk16, Abderrahim Farina16, Susan Faro16, Diallo Ferguson16, Patricia Ferreira16, Sheila Fisher16, Mike FitzGerald16, Karen Foley16, Chelsea Foley16, Alicia Franke16, Dennis Friedrich16, Diane Gage16, Manuel Garber16, Gary Gearin16, Georgia Giannoukos16, Tina Goode16, Audra Goyette16, Joseph Graham16, Edward Grandbois16, Kunsang Gyaltsen16, Nabil Hafez16, Daniel Hagopian16, Birhane Hagos16, Jennifer Hall16, Claire Healy16, Ryan Hegarty16, Tracey Honan16, Andrea Horn16, Nathan Houde16, Leanne Hughes16, Leigh Hunnicutt16, M. Husby16, Benjamin Jester16, Charlien Jones16, Asha Kamat16, Ben Kanga16, Cristyn Kells16, Dmitry Khazanovich16, Alix Chinh Kieu16, Peter Kisner16, Mayank Kumar16, Krista Lance16, Thomas Landers16, Marcia Lara16, William Lee16, Jean-Pierre Leger16, Niall Lennon16, Lisa Leuper16, Sarah LeVine16, Jinlei Liu16, Xiaohong Liu16, Yeshi Lokyitsang16, Tashi Lokyitsang16, Annie Lui16, Jan Macdonald16, John Major16, Richard Marabella16, Kebede Maru16, Charles Matthews16, Susan McDonough16, Teena Mehta16, James Meldrim16, Alexandre Melnikov16, Louis Meneus16, Atanas Mihalev16, Tanya Mihova16, Karen Miller16, Rachel Mittelman16, Valentine Mlenga16, Leonidas Mulrain16, Glen Munson16, Adam Navidi16, Jerome Naylor16, Tuyen Nguyen16, Nga Nguyen16, Cindy Nguyen16, Thu Nguyen16, Robert Nicol16, Nyima Norbu16, Choe Norbu16, Nathaniel Novod16, Tenchoe Nyima16, Peter Olandt16, Barry O'Neill16, Keith O'Neill16, Sahal Osman16, Lucien Oyono16, Christopher Patti16, Danielle Perrin16, Pema Phunkhang16, Fritz Pierre16, Margaret Priest16, Anthony Rachupka16, Sujaa Raghuraman16, Rayale Rameau16, Verneda Ray16, Christina Raymond16, Filip Rege16, Cecil Rise16, Julie Rogers16, Peter Rogov16, Julie Sahalie16, Sampath Settipalli16, Theodore Sharpe16, Terrance Shea16, Mechele Sheehan16, Ngawang Sherpa16, Jianying Shi16, Diana Shih16, Jessie Sloan16, Cherylyn Smith16, Todd Sparrow16, John Stalker1, Nicole Stange-Thomann16, Sharon Stavropoulos16, Catherine Stone16, Sabrina Stone16, Sean Sykes16, Pierre Tchuinga16, Pema Tenzing16, Senait Tesfaye16, Dawa Thoulutsang16, Yama Thoulutsang16, Kerri Topham16, Ira Topping16, Tsamla Tsamla16, Helen Vassiliev16, Vijay Venkataraman16, Andy Vo16, Tsering Wangchuk16, Tsering Wangdi16, Michael Weiand16, Jane Wilkinson16, Adam Wilson16, Shailendra Yadav16, Shuli Yang16, Xiaoping Yang16, Geneva Young16, Qing Yu16, Joanne Zainoun16, Lisa Zembek16 & Andrew Zimmer16 for Broad Sequencing Platform members & Eric S. Lander1,15

  1. Broad Institute of Harvard and MIT, 320 Charles Street, Cambridge, Massachusetts 02141, USA
  2. Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
  3. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  4. Program in Bioinformatics, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA
  5. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
  6. Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA
  7. National Human Genome Research Institute, National Institutes of Health, 50 South Drive, MSC 8000, Building 50, Bethesda, Maryland 20892-8000, USA
  8. MRC Functional Genetics, University of Oxford, Department of Human Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK
  9. UMR 6061 Genetique et Developpement, CNRS—Université de Rennes 1, Faculté de Médecine, 2, Avenue Leon Bernard, 35043 Rennes Cedex, France
  10. Agencourt Bioscience Corporation, 500 Cummings Center, Suite 2450, Beverly, Massachusetts 01915, USA
  11. Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, California 94609, USA
  12. The Institute for Genomic Research, Rockville, Maryland 20850, USA
  13. Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA
  14. The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  15. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
  16. Broad Institute of Harvard and MIT, 320 Charles Street, Cambridge, Massachusetts 02141, USA
  17. *A list of participants and affiliations appears at the end of the paper.

Correspondence to: Kerstin Lindblad-Toh1Eric S. Lander1,15 Correspondence and requests for materials should be addressed to K.L.T. (Email: kersli@broad.mit.edu) or E.S.L. (Email: lander@broad.mit.edu). The draft genome sequence has been deposited in public databases under NCBI accession codes AAEX01000000 (CanFam1.0) and AAEX02000000 (CanFam2.0). SNPs have been deposited in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP/).

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Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

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