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      Genomic Prediction Within and Across Biparental Families: Means and Variances of Prediction Accuracy and Usefulness of Deterministic Equations

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          Abstract

          A major application of genomic prediction (GP) in plant breeding is the identification of superior inbred lines within families derived from biparental crosses. When models for various traits were trained within related or unrelated biparental families (BPFs), experimental studies found substantial variation in prediction accuracy (PA), but little is known about the underlying factors. We used SNP marker genotypes of inbred lines from either elite germplasm or landraces of maize ( Zea mays L.) as parents to generate in silico 300 BPFs of doubled-haploid lines. We analyzed PA within each BPF for 50 simulated polygenic traits, using genomic best linear unbiased prediction (GBLUP) models trained with individuals from either full-sib (FSF), half-sib (HSF), or unrelated families (URF) for various sizes ( N t r a i n ) of the training set and different heritabilities ( h 2 ) . In addition, we modified two deterministic equations for forecasting PA to account for inbreeding and genetic variance unexplained by the training set. Averaged across traits, PA was high within FSF (0.41–0.97) with large variation only for N t r a i n < 50 and h 2 < 0.6. For HSF and URF, PA was on average ∼40–60% lower and varied substantially among different combinations of BPFs used for model training and prediction as well as different traits. As exemplified by HSF results, PA of across-family GP can be very low if causal variants not segregating in the training set account for a sizeable proportion of the genetic variance among predicted individuals. Deterministic equations accurately forecast the PA expected over many traits, yet cannot capture trait-specific deviations. We conclude that model training within BPFs generally yields stable PA, whereas a high level of uncertainty is encountered in across-family GP. Our study shows the extent of variation in PA that must be at least reckoned with in practice and offers a starting point for the design of training sets composed of multiple BPFs.

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          Most cited references39

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          Introduction to Quantitative Genetics

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            Development and Characterization of a High Density SNP Genotyping Assay for Cattle

            The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of <350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative copy number variants in cattle. Utility for GWA was demonstrated by localizing known variation for coat color and the presence/absence of horns to their correct genomic locations. The combination of SNP selection and the novel spacing algorithm allows an efficient approach for the development of high-density genotyping platforms in species having full or even moderate quality draft sequence. Aspects of the approach can be exploited in species which lack an available genome sequence. The BovineSNP50 assay described here is commercially available from Illumina and provides a robust platform for mapping disease genes and QTL in cattle.
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              Accuracy of Predicting the Genetic Risk of Disease Using a Genome-Wide Approach

              Background The prediction of the genetic disease risk of an individual is a powerful public health tool. While predicting risk has been successful in diseases which follow simple Mendelian inheritance, it has proven challenging in complex diseases for which a large number of loci contribute to the genetic variance. The large numbers of single nucleotide polymorphisms now available provide new opportunities for predicting genetic risk of complex diseases with high accuracy. Methodology/Principal Findings We have derived simple deterministic formulae to predict the accuracy of predicted genetic risk from population or case control studies using a genome-wide approach and assuming a dichotomous disease phenotype with an underlying continuous liability. We show that the prediction equations are special cases of the more general problem of predicting the accuracy of estimates of genetic values of a continuous phenotype. Our predictive equations are responsive to all parameters that affect accuracy and they are independent of allele frequency and effect distributions. Deterministic prediction errors when tested by simulation were generally small. The common link among the expressions for accuracy is that they are best summarized as the product of the ratio of number of phenotypic records per number of risk loci and the observed heritability. Conclusions/Significance This study advances the understanding of the relative power of case control and population studies of disease. The predictions represent an upper bound of accuracy which may be achievable with improved effect estimation methods. The formulae derived will help researchers determine an appropriate sample size to attain a certain accuracy when predicting genetic risk.
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                Author and article information

                Journal
                G3 (Bethesda)
                Genetics
                G3: Genes, Genomes, Genetics
                G3: Genes, Genomes, Genetics
                G3: Genes, Genomes, Genetics
                G3: Genes|Genomes|Genetics
                Genetics Society of America
                2160-1836
                15 September 2017
                November 2017
                : 7
                : 11
                : 3571-3586
                Affiliations
                [* ]Institute of Plant Breeding, Seed Science and Population Genetics, University of Hohenheim, 70599 Stuttgart, Germany
                []Animal Breeding and Genomics, Wageningen University and Research, 6700 AH, The Netherlands
                Author notes

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                [1 ]Corresponding author: Institute of Plant Breeding, Seed Sciences and Population Genetics, University of Hohenheim, Fruwirthstrasse 21, 70599 Stuttgart, Germany. E-mail: melchinger@ 123456uni-hohenheim.de
                Article
                GGG_300076
                10.1534/g3.117.300076
                5677162
                28916649
                0849fde5-6ce4-4746-9cce-ec7270445509
                Copyright © 2017 Schopp et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 July 2017
                : 22 August 2017
                Page count
                Figures: 4, Tables: 2, Equations: 32, References: 58, Pages: 16
                Categories
                Genomic Selection

                Genetics
                genomic prediction,biparental families,plant breeding,gblup,deterministic accuracy,linkage disequilibrium,genpred,shared data resources,genomic selection

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