Copy number variation underlies complex phenotypes in domestic dog breeds and other canids
- Aitor Serres-Armero1,
- Brian W. Davis2,3,
- Inna S. Povolotskaya4,
- Carlos Morcillo-Suarez1,
- Jocelyn Plassais2,
- David Juan1,
- Elaine A. Ostrander2 and
- Tomas Marques-Bonet1,5,6,7
- 1IBE, Institut de Biologia Evolutiva (Universitat Pompeu Fabra/CSIC), Ciencies Experimentals i de la Salut, Barcelona 08003, Spain;
- 2Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 3Department of Veterinary Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843, USA;
- 4Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow 117997, Russia;
- 5CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Barcelona 08028, Spain;
- 6Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia 08010, Spain;
- 7Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Catalonia 08201, Spain
Abstract
Extreme phenotypic diversity, a history of artificial selection, and socioeconomic value make domestic dog breeds a compelling subject for genomic research. Copy number variation (CNV) is known to account for a significant part of inter-individual genomic diversity in other systems. However, a comprehensive genome-wide study of structural variation as it relates to breed-specific phenotypes is lacking. We have generated whole genome CNV maps for more than 300 canids. Our data set extends the canine structural variation landscape to more than 100 dog breeds, including novel variants that cannot be assessed using microarray technologies. We have taken advantage of this data set to perform the first CNV-based genome-wide association study (GWAS) in canids. We identify 96 loci that display copy number differences across breeds, which are statistically associated with a previously compiled set of breed-specific morphometrics and disease susceptibilities. Among these, we highlight the discovery of a long-range interaction involving a CNV near MED13L and TBX3, which could influence breed standard height. Integration of the CNVs with chromatin interactions, long noncoding RNA expression, and single nucleotide variation highlights a subset of specific loci and genes with potential functional relevance and the prospect to explain trait variation between dog breeds.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.266049.120.
-
Freely available online through the Genome Research Open Access option.
- Received May 15, 2020.
- Accepted February 26, 2021.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
