Evaluation of Whole-Genome Sequence Imputation Strategies in Korean Hanwoo Cattle

SIMPLE SUMMARY: In this study, we evaluated various imputation strategies for the Korean Hanwoo cattle. We observed that a large reference panel consisting of many cattle breeds did not improve the imputation accuracy when compared to a proportionally small purebred Hanwoo reference. This was because the multi-breed reference did not contain animals sufficiently related to the Hanwoo to improve the accuracies and, although not detrimental, in effect, only added to the computational burden of the imputation. Despite the large multi-breed reference, when the Hanwoo were removed from the reference, the imputation accuracies were low. These results suggest additional sequencing efforts are needed for underrepresented breeds, particularly those less genetically related to the main European breeds. ABSTRACT: This study evaluated the accuracy of sequence imputation in Hanwoo beef cattle using different reference panels: a large multi-breed reference with no Hanwoo (n = 6269), a much smaller Hanwoo purebred reference (n = 88), and both datasets combined (n = 6357). The target animals were 136 cattle both sequenced and genotyped with the Illumina BovineSNP50 v2 (50K). The average imputation accuracy measured by the Pearson correlation (R) was 0.695 with the multi-breed reference, 0.876 with the purebred Hanwoo, and 0.887 with the combined data; the average concordance rates (CR) were 88.16%, 94.49%, and 94.84%, respectively. The accuracy gains from adding a large multi-breed reference of 6269 samples to only 88 Hanwoo was marginal; however, the concordance rate for the heterozygotes decreased from 85% to 82%, and the concordance rate for fixed SNPs in Hanwoo also decreased from 99.98% to 98.73%. Although the multi-breed panel was large, it was not sufficiently representative of the breed for accurate imputation without the Hanwoo animals. Additionally, we evaluated the value of high-density 700K genotypes (n = 991) as an intermediary step in the imputation process. The imputation accuracy differences were negligible between a single-step imputation strategy from 50K directly to sequence and a two-step imputation approach (50K-700K-sequence). We also observed that imputed sequence data can be used as a reference panel for imputation (mean R = 0.9650, mean CR = 98.35%). Finally, we identified 31 poorly imputed genomic regions in the Hanwoo genome and demonstrated that imputation accuracies were particularly lower at the chromosomal ends.