Article
Nature 438, 803-819 (8 December 2005) | doi:10.1038/nature04338
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
Broad Sequencing Platform members
and Eric S. Lander1,15Abstract
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.
- Broad Institute of Harvard and MIT, 320 Charles Street, Cambridge, Massachusetts 02141, USA
- Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
- Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Program in Bioinformatics, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA
- Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
- Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California 90095, USA
- National Human Genome Research Institute, National Institutes of Health, 50 South Drive, MSC 8000, Building 50, Bethesda, Maryland 20892-8000, USA
- MRC Functional Genetics, University of Oxford, Department of Human Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK
- UMR 6061 Genetique et Developpement, CNRS—Université de Rennes 1, Faculté de Médecine, 2, Avenue Leon Bernard, 35043 Rennes Cedex, France
- Agencourt Bioscience Corporation, 500 Cummings Center, Suite 2450, Beverly, Massachusetts 01915, USA
- Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, California 94609, USA
- The Institute for Genomic Research, Rockville, Maryland 20850, USA
- Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA
- The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
- Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
- Broad Institute of Harvard and MIT, 320 Charles Street, Cambridge, Massachusetts 02141, USA
- *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/).
Received 9 August 2005; Accepted 11 October 2005
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