The genomic architecture of segmental duplications and associated copy number variants in dogs
- Thomas J. Nicholas1,
- Ze Cheng1,2,
- Mario Ventura3,
- Katrina Mealey4,
- Evan E. Eichler1,2,5 and
- Joshua M. Akey1,5
- 1 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
- 2 Howard Hughes Medical Institute, Seattle, Washington 98195, USA;
- 3 Department of Genetics and Microbiology, University of Bari, 70124 Bari, Italy;
- 4 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164-6610, USA
Abstract
Structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of segmental duplications and associated copy number variants (CNVs) in the modern domesticated dog, Canis familiaris, which exhibits considerable morphological, physiological, and behavioral variation. Through computational analyses of the publicly available canine reference sequence, we estimate that segmental duplications comprise ∼4.21% of the canine genome. Segmental duplications overlap 841 genes and are significantly enriched for specific biological functions such as immunity and defense and KRAB box transcription factors. We designed high-density tiling arrays spanning all predicted segmental duplications and performed aCGH in a panel of 17 breeds and a gray wolf. In total, we identified 3583 CNVs, ∼68% of which were found in two or more samples that map to 678 unique regions. CNVs span 429 genes that are involved in a wide variety of biological processes such as olfaction, immunity, and gene regulation. Our results provide insight into mechanisms of canine genome evolution and generate a valuable resource for future evolutionary and phenotypic studies.
Footnotes
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↵5 Corresponding authors.
↵E-mail akeyj{at}u.washington.edu; fax (206) 685-7301.
↵E-mail eee{at}gs.washington.edu; fax (206) 685-7301.
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[Supplemental material is available online at www.genome.org. All aCGH data from this study have been submitted to Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) under accession no. GSE13266.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.084715.108.
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- Received August 12, 2008.
- Accepted December 17, 2008.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press
