Incorporation of causative quantitative trait nucleotides in single-step GBLUP

• Published in: Genetics selection evolution (Paris) 2017-07, Vol.49 (1), p.59-59, Article 59
• Main Authors: Fragomeni, Breno O, Lourenco, Daniela A L, Masuda, Yutaka, Legarra, Andres, Misztal, Ignacy
• Format: Article
• Language: English
• Subjects: Accuracy; Algorithms; Animal breeding; Animals; Blending; Breeding; Cattle; Chromosomes; Computation; Computer Simulation; Dairy cattle; Eigenvalues; Gene polymorphism; Genes; Genetic diversity; Genetic variance; Genome - genetics; Genome-Wide Association Study; Genomes; Genomics; Genotype; Genotypes; Life Sciences; Linear systems; Livestock; Models, Genetic; Nucleotides; Nucleotides - genetics; Pedigree; Phenotype; Phenotypes; Polymorphism; Polymorphism, Single Nucleotide; Quantitative Trait Loci - genetics; Simulation; Single nucleotide polymorphisms; Single-nucleotide polymorphism
• ISSN: 1297-9686; 0999-193X; 1297-9686
• DOI: 10.1186/s12711-017-0335-0

Much effort is put into identifying causative quantitative trait nucleotides (QTN) in animal breeding, empowered by the availability of dense single nucleotide polymorphism (SNP) information. Genomic selection using traditional SNP information is easily implemented for any number of genotyped individuals using single-step genomic best linear unbiased predictor (ssGBLUP) with the algorithm for proven and young (APY). Our aim was to investigate whether ssGBLUP is useful for genomic prediction when some or all QTN are known. Simulations included 180,000 animals across 11 generations. Phenotypes were available for all animals in generations 6 to 10. Genotypes for 60,000 SNPs across 10 chromosomes were available for 29,000 individuals. The genetic variance was fully accounted for by 100 or 1000 biallelic QTN. Raw genomic relationship matrices (GRM) were computed from (a) unweighted SNPs, (b) unweighted SNPs and causative QTN, (c) SNPs and causative QTN weighted with results obtained with genome-wide association studies, (d) unweighted SNPs and causative QTN with simulated weights, (e) only unweighted causative QTN, (f-h) as in (b-d) but using only the top 10% causative QTN, and (i) using only causative QTN with simulated weight. Predictions were computed by pedigree-based BLUP (PBLUP) and ssGBLUP. Raw GRM were blended with 1 or 5% of the numerator relationship matrix, or 1% of the identity matrix. Inverses of GRM were obtained directly or with APY. Accuracy of breeding values for 5000 genotyped animals in the last generation with PBLUP was 0.32, and for ssGBLUP it increased to 0.49 with an unweighted GRM, 0.53 after adding unweighted QTN, 0.63 when QTN weights were estimated, and 0.89 when QTN weights were based on true effects known from the simulation. When the GRM was constructed from causative QTN only, accuracy was 0.95 and 0.99 with blending at 5 and 1%, respectively. Accuracies simulating 1000 QTN were generally lower, with a similar trend. Accuracies using the APY inverse were equal or higher than those with a regular inverse. Single-step GBLUP can account for causative QTN via a weighted GRM. Accuracy gains are maximum when variances of causative QTN are known and blending is at 1%.