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 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 ...

家犬的基因组学研究资源随着173k SNP阵列（SNP array）平台的广泛应用以及更新版参考基因组的推出而得到显著优化。该密度的SNP阵列足以检测品种内的遗传关联，但在跨多个品种或混种犬的关联分析中统计效力不足——此类群体中标记间的连锁不平衡（linkage disequilibrium）衰减速度极快，尽管这类研究对复杂疾病与性状的遗传定位具有重要的应用前景。本研究构建了一套基因型填充参考面板（imputation reference panel），包含365个经过全基因组测序的多样化家犬与灰狼样本，可将全基因组关联研究（genome-wide association studies, GWAS）中可检测的遗传标记数量提升约130倍。利用已完成基因分型的犬只样本，我们验证了该参考面板的实用性：其可识别潜在的新型关联位点，包括一个与犬颅十字韧带病（cranial cruciate ligament disease）显著相关的CFA20染色体区域，并可对犬体型及血液表型进行精细定位，即便当……