Joint imputation of whole-genome sequence variants and large chromosomal deletions in cattle

Abstract

Genotype imputation, often focused on SNP and small insertions and deletions (indels; size ≤50 bp), is a crucial step for association mapping and estimation of genomic breeding values. Here, we present strategies to impute genotypes for large chromosomal deletions (size >50 bp), along with SNP and indels in cattle. The pipelines include a strategy for extending the whole-genome sequence reference panel for large deletions, a 2-step genotype refinement approach using Beagle4 and SHAPEIT2 software, and finally, joint imputation of SNP, indels, and large deletions to the existing SNP array-typed population using Minimac3 software. Using these pipelines we achieved an imputation accuracy of the squared Pearson correlation (r2) > 0.6 at minor allele frequencies as low as 0.7% for SNP and indels, and 0.2% for large deletions. This highlights the potential of our approach to build a haplotype reference panel and impute different classes of sequence variants across a wide allele frequency spectrum with high accuracy.