Imputation accuracy to whole-genome sequence in Nellore cattle

Author(s)

Fernandes Junior, Gerardo A. ^[1] ; Carvalheiro, Roberto ^{[1, 2]} ; de Oliveira, Henrique N. ^{[1, 2]} ; Sargolzaei, Mehdi ^{[3, 4]} ; Costilla, Roy ^[5] ; Ventura, Ricardo V. ^[6] ; Fonseca, Larissa F. S. ^[1] ; Neves, Haroldo H. R. ^[7] ; Hayes, Ben J. ^[5] ; de Albuquerque, Lucia G. ^{[1, 2]}

Affiliation

^[1] UNESP, Sch Agr & Vet Sci, BR-14884900 Jaboticabal, SP - Brazil

^[2] CNPq, Natl Council Sci & Technol Dev, BR-71605001 Brasilia, DF - Brazil

^[3] Ontario Vet Coll, Guelph, ON - Canada

^[4] Select Sires Inc, Plain City, OH - USA

^[5] UQ, Queensland Alliance Agr & Food Innovat, Brisbane, Qld - Australia

^[6] Univ Sao Paulo, Sch Vet Med & Anim Sci, BR-13635900 Pirassununga, SP - Brazil

^[7] Gensys Associated Consultants, BR-90680000 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: GENETICS SELECTION EVOLUTION; v. 53, n. 1 MAR 12 2021.
• Web of Science Citations: 0

Abstract

BackgroundA cost-effective strategy to explore the complete DNA sequence in animals for genetic evaluation purposes is to sequence key ancestors of a population, followed by imputation mechanisms to infer marker genotypes that were not originally reported in a target population of animals genotyped with single nucleotide polymorphism (SNP) panels. The feasibility of this process relies on the accuracy of the genotype imputation in that population, particularly for potential causal mutations which may be at low frequency and either within genes or regulatory regions. The objective of the present study was to investigate the imputation accuracy to the sequence level in a Nellore beef cattle population, including that for variants in annotation classes which are more likely to be functional.MethodsInformation of 151 key sequenced Nellore sires were used to assess the imputation accuracy from bovine HD BeadChip SNP (similar to 777 k) to whole-genome sequence. The choice of the sires aimed at optimizing the imputation accuracy of a genotypic database, comprised of about 10,000 genotyped Nellore animals. Genotype imputation was performed using two computational approaches: FImpute3 and Minimac4 (after using Eagle for phasing). The accuracy of the imputation was evaluated using a fivefold cross-validation scheme and measured by the squared correlation between observed and imputed genotypes, calculated by individual and by SNP. SNPs were classified into a range of annotations, and the accuracy of imputation within each annotation classification was also evaluated.ResultsHigh average imputation accuracies per animal were achieved using both FImpute3 (0.94) and Minimac4 (0.95). On average, common variants (minor allele frequency (MAF)>0.03) were more accurately imputed by Minimac4 and low-frequency variants (MAF <= 0.03) were more accurately imputed by FImpute3. The inherent Minimac4 Rsq imputation quality statistic appears to be a good indicator of the empirical Minimac4 imputation accuracy. Both software provided high average SNP-wise imputation accuracy for all classes of biological annotations.ConclusionsOur results indicate that imputation to whole-genome sequence is feasible in Nellore beef cattle since high imputation accuracies per individual are expected. SNP-wise imputation accuracy is software-dependent, especially for rare variants. The accuracy of imputation appears to be relatively independent of annotation classification. (AU)

• FAPESP's process: 17/10630-2 - Genetic aspects of meat production quality, efficiency and sustainability in Nelore breed animals
• Grantee: Lucia Galvão de Albuquerque
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/12434-1 - Imputation accuracy to whole genome sequence in Nellore beef cattle
• Grantee: Gerardo Alves Fernandes Júnior
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 09/16118-5 - Genomic tools to genetic improvement of direct economic important traits in Nelore cattle
• Grantee: Lucia Galvão de Albuquerque
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/10109-3 - Identification and analysis of genetic variants obtained from the whole-genome sequencing of Nellore bulls
• Grantee: Gerardo Alves Fernandes Júnior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/20026-8 - Multi-user equipment approved in grant 2017/10630-2: server
• Grantee: Lucia Galvão de Albuquerque
• Support Opportunities: Multi-user Equipment Program