Improving the resolution of canine genome‐wide association studies using genotype imputation: A study of two breeds

Abstract

Summary Genotype imputation using a reference panel that combines high‐density array data and publicly available whole genome sequence consortium variant data is potentially a cost‐effective method to increase the density of extant lower‐density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed‐specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R2 = 0.94) and the highest for the Italian Spinone dataset (mean R2 = 0.97). This study’s findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed‐specific array data and multi‐breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed‐specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.

Whole Genome Sequencing Reveals Multiple Linked Genetic Variants on Canine Chromosome 12 Associated with Risk for Symmetrical Lupoid Onychodystrophy (SLO) in the Bearded Collie

“…Genotype imputation of WGS variants was employed on the 82 unrelated Bearded Collies included in the previous GWAS in an effort to refine the list of variants for further exploration. Imputation accuracy, estimated as the percentage of correctly imputed genotypes in 24 Bearded Collies, averaged 91.7% for SNPs (range 81.3-98.3%) and 87.6% for insertions or deletions (i.e., indels; range 78.5-97.8%) on CFA12, and 86.8% for SNPs (range 75.1-99.4%) and 84.6% for indels (range 73.0-98.9%) on CFA17, similar to what has previously been achieved with a multi-breed reference panel [16][17][18].…”

“…The purpose of this study was to explore whole genome sequencing (WGS) data from SLO-affected and healthy Bearded Collies in order to identify putative causative variants within the two GWAS-associated regions on CFA12 and CFA17. To refine the large number of WGS variants observed in the regions of interest, genotype imputation, which has been shown to accurately predict WGS genotypes based on data from high-density SNP arrays [16][17][18], was also employed.…”

Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture

“…While this study suggested discarding sites with a MAF < 0.05, our data argues for selecting variants with imputation quality > 0.90 and reference MAFs > 1%. This reflects both the large number of dogs and breeds as well as the variation captured in village dogs in our dataset, both of which are critical for the development of any reference panel, in dogs [ 119 , 120 ] or otherwise [ 121 ]. For the Illumina CanineHD BeadChip platform, the criteria we propose will provide imputed genotypes with NRC rates > 0.85 for over 8 M sites, whereas for the low-pass WGS and Axiom Canine HD Array platforms, these criteria provide NRC rates of approximately 0.95 for over 10 M sites (Fig.…”

Imputation of ancient canid genomes reveals inbreeding history over the past 10,000 years

“…However, species with reference panels lacking ancestral diversity show reduced accuracy (e.g., pigs) (Erven et al 2022). Imputation of modern dogs has shown promising results as a method to increase SNP density (Hayward et al 2016, 2019; Jenkins et al 2021; Buckley et al 2022; Morrill et al 2022; Meadows et al 2023), but the accuracy of imputation has not been previously investigated for ancient canids, nor have results from such been applied to questions of canine migration or domestication.…”