Division of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
Animal and Veterinary Sciences Group, Scotland's Rural College, Edinburgh, EH9 3JG, UK.
Anim Genet. 2018 Aug;49(4):303-311. doi: 10.1111/age.12677. Epub 2018 Jul 5.
The dog is a valuable model species for the genetic analysis of complex traits, and the use of genotype imputation in dogs will be an important tool for future studies. It is of particular interest to analyse the effect of factors like single nucleotide polymorphism (SNP) density of genotyping arrays and relatedness between dogs on imputation accuracy due to the acknowledged genetic and pedigree structure of dog breeds. In this study, we simulated different genotyping strategies based on data from 1179 Labrador Retriever dogs. The study involved 5826 SNPs on chromosome 1 representing the high density (HighD) array; the low-density (LowD) array was simulated by masking different proportions of SNPs on the HighD array. The correlations between true and imputed genotypes for a realistic masking level of 87.5% ranged from 0.92 to 0.97, depending on the scenario used. A correlation of 0.92 was found for a likely scenario (10% of dogs genotyped using HighD, 87.5% of HighD SNPs masked in the LowD array), which indicates that genotype imputation in Labrador Retrievers can be a valuable tool to reduce experimental costs while increasing sample size. Furthermore, we show that genotype imputation can be performed successfully even without pedigree information and with low relatedness between dogs in the reference and validation sets. Based on these results, the impact of genotype imputation was evaluated in a genome-wide association analysis and genomic prediction in Labrador Retrievers.
狗是用于分析复杂性状的遗传分析的有价值的模式物种，基因型推断在狗中的应用将成为未来研究的重要工具。由于狗品种的公认遗传和系谱结构，分析因素（如基因分型阵列的单核苷酸多态性（SNP）密度和狗之间的亲缘关系）对推断准确性的影响特别有趣。在这项研究中，我们根据 1179 只拉布拉多猎犬的数据模拟了不同的基因分型策略。研究涉及代表高密度（HighD）阵列的 1 号染色体上的 5826 个 SNP；通过掩蔽 HighD 阵列上不同比例的 SNP 来模拟低密度（LowD）阵列。在实际掩蔽水平为 87.5％的情况下，真实基因型和推断基因型之间的相关性在 0.92 到 0.97 之间变化，具体取决于使用的方案。在可能的情况下（10％的狗使用 HighD 进行基因分型，87.5％的 HighD SNP 在 LowD 阵列中被掩蔽），发现了 0.92 的相关性，这表明在拉布拉多猎犬中，基因型推断可以是一种有价值的工具，可在降低实验成本的同时增加样本量。此外，我们还表明，即使没有系谱信息，并且参考和验证集中的狗之间的亲缘关系较低，也可以成功进行基因型推断。基于这些结果，在拉布拉多猎犬的全基因组关联分析和基因组预测中评估了基因型推断的影响。
