Assessment of the functionality of genome-wide canine SNP arrays and implications for canine disease association studies.
Domestic dogs share a wide range of important disease conditions with humans, including cancers, diabetes and epilepsy. Many of these conditions have similar or identical underlying pathologies to their human counterparts and thus dogs represent physiologically relevant natural models of human disorders. Comparative genomic approaches whereby disease genes can be identified in dog diseases and then mapped onto the human genome are now recognized as a valid method and are increasing in popularity. The majority of dog breeds have been created over the past few hundred years and, as a consequence, the dog genome is characterized by extensive linkage disequilibrium (LD), extending usually from hundreds of kilobases to several megabases within a breed, rather than tens of kilobases observed in the human genome. Genome-wide canine SNP arrays have been developed, and increasing success of using these arrays to map disease loci in dogs is emerging. No equivalent of the human HapMap currently exists for different canine breeds, and the LD structure for such breeds is far less understood than for humans. This study is a dedicated large-scale assessment of the functionalities (LD and SNP tagging performance) of canine genome-wide SNP arrays in multiple domestic dog breeds. We have used genotype data from 18 breeds as well as wolves and coyotes genotyped by the Illumina 22K canine SNP array and Affymetrix 50K canine SNP array. As expected, high tagging performance was observed with most of the breeds using both Illumina and Affymetrix arrays when multi-marker tagging was applied. In contrast, however, large differences in population structure, LD coverage and pairwise tagging performance were found between breeds, suggesting that study designs should be carefully assessed for individual breeds before undertaking genome-wide association studies (GWAS).
Centre for Integrated Genomic Medical Research, School of Medicine, University of Manchester, Oxford Road, Manchester, UKInstitute of Child Health, University College London, 30 Guilford Street, London, UKDepartment of Veterinary Biosciences, Department of Medical Genetics and Program in Molecular Medicine, Folkhälsan Research Center, Haartmaninkatu 8, 00014 University of Helsinki, FinlandDepartment of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool, UKRoyal (Dick) School of Veterinary Studies, Division of Veterinary Clinical Sciences, The University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian, Scotland, EH25 9RG, UKInstitute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, USA.
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L J
LJ
Kennedy
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Short
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Seppälä
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Barnes
D N
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Clements
S H
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Wood
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SD
Carter
G M
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Happ
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Lohi
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Ollier
D000818:Animals; D001947:Breeding; D002874:Chromosome Mapping / Q000662:veterinary; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D016678:Genome / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000662:veterinary; D005838:Genotype; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013045:Species Specificity