Assessment of imputation from low-pass sequencing to predict merit of beef steers

Authors: Snelling, Warren; HOFF, JESSE - GENCOVE, INC.; LI, JEREMIAH - GENCOVE, INC.; Kuehn, Larry; Keel, Brittney; Lindholm-Perry, Amanda; PICKRELL, JOSEPH - GENCOVE, INC.

Submitted to: Genes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2020
Publication Date: 11/5/2020
Citation: Snelling, W.M., Hoff, J.L., Li, J.H., Kuehn, L.A., Keel, B.N., Lindholm-Perry, A.K., Pickrell, J.K. 2020. Assessment of imputation from low-pass sequencing to predict merit of beef steers. Genes. 11(11). Article 1312. https://doi.org/10.3390/genes11111312.
DOI: https://doi.org/10.3390/genes11111312

Interpretive Summary: It is now possible to obtain a small amount of DNA sequence on many animals at a cost similar to the cost of genotyping those animals with a commercially available SNP array. If individual genotypes can be imputed accurately from that sequence, an approach using low-pass sequencing with imputation may be an attractive alternative to genotyping with SNP arrays. This study used existing sequence data from 77 steers to mimic low-pass sequencing and evaluate imputation accuracy and agreement between genomic breeding values using genotypes from SNP array or imputed from low-pass sequence. High correlations (>0.95) between imputed and SNP assay genotypes were observed, and breeding values predicted by applying SNP effects to imputed or SNP assay genotypes were similar. Low-pass sequencing with imputation may provide genotypes for a much more comprehensive set of variants than can be genotyped with a SNP array.

Technical Abstract: Decreasing costs are making low coverage sequencing with imputation to a comprehensive reference panel an attractive alternative to obtain functional variant genotypes that can increase the accuracy of genomic prediction. To assess the potential of low-pass sequencing, genomic sequence of 77 steers sequenced to >10X coverage was downsampled to 1X and imputed to a reference of 946 cattle representing multiple Bos taurus and Bos indicus-influenced breeds. Genotypes for nearly 60 million variants detected in the reference were imputed from downsampled sequence. The imputed genotypes strongly agreed with SNP array genotypes (r ¯=0.99) and the genotypes called from transcript sequence (r ¯=0.97). Effects of BovineSNP50 and GGP-F250 variants on birth weight, postweaning gain and marbling were solved without the steers’ phenotypes and genotypes, then applied to their genotypes to predict molecular breeding values (MBV). The steers’ MBV were similar when using imputed and array genotypes. Replacing array variants with functional sequence variants may allow more robust MBV. Imputation from low coverage sequence offers a viable, low-cost approach to obtain functional variant genotypes that could improve genomic prediction.