Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies
Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds...
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| Veröffentlicht in: | PLoS genetics 2019-09, Vol.15 (9), p.e1008003 |
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| creator | Hayward, Jessica J White, Michelle E Boyle, Michael Shannon, Laura M Casal, Margret L Castelhano, Marta G Center, Sharon A Meyers-Wallen, Vicki N Simpson, Kenneth W Sutter, Nathan B Todhunter, Rory J Boyko, Adam R |
| description | Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying potentially novel associations, including a locus on CFA20 significantly associated with cranial cruciate ligament disease, and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibrium with any single array marker. This reference panel resource will improve future genome-wide association studies for canine complex diseases and other phenotypes. |
| doi_str_mv | 10.1371/journal.pgen.1008003 |
| format | Article |
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SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying potentially novel associations, including a locus on CFA20 significantly associated with cranial cruciate ligament disease, and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibrium with any single array marker. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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| subjects | Animals Anterior cruciate ligament Beef cattle Biology and Life Sciences Body size Breeding Chromosome Mapping - methods Disease DNA sequencing Dogs Dogs - genetics Funding Gene mapping Genetic aspects Genetic research Genome - genetics Genome-wide association studies Genome-Wide Association Study - methods Genomes Genomics Genomics - methods Genotype Genotype & phenotype Genotypes Gray wolf Haplotypes Ligaments Linkage disequilibrium Linkage Disequilibrium - genetics Medical research Medicine and Health Sciences Methods Morphology Multiple imputation (Statistics) Novels Phenotype Phenotypes Polymorphism, Single Nucleotide - genetics Power Single-nucleotide polymorphism Software Veterinary colleges Veterinary medicine Whole Genome Sequencing - methods |
| title | Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies |
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