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Improving genomic predictions by correction of genotypes from genotyping by sequencing in livestock populations.

ABSTRACT: Background:Genotyping by sequencing (GBS) is a robust method to genotype markers. Many factors can influence the genotyping quality. One is that heterozygous genotypes could be wrongly genotyped as homozygotes, dependent on the genotyping depths. In this study, a method correcting this type of genotyping error was demonstrated. The efficiency of this correction method and its effect on genomic prediction were assessed using simulated data of livestock populations. Results:Chip array (Chip) and four depths of GBS data was simulated. After quality control (call rate???0.8 and MAF???0.01), the remaining number of Chip and GBS SNPs were both approximately 7,000, averaged over 10 replicates. GBS genotypes were corrected with the proposed method. The reliability of genomic prediction was calculated using GBS, corrected GBS (GBSc), true genotypes for the GBS loci (GBSr) and Chip data. The results showed that GBSc had higher rates of correct genotype calls and higher correlations with true genotypes than GBS. For genomic prediction, using Chip data resulted in the highest reliability. As the depth increased to 10, the prediction reliabilities using GBS and GBSc data approached those using true GBS data. The reliabilities of genomic prediction using GBSc data were 0.604, 0.672, 0.684 and 0.704 after genomic correction, with the improved values of 0.013, 0.009, 0.006 and 0.001 at depth?=?2, 4, 5 and 10, respectively. Conclusions:The current study showed that a correction method for GBS data increased the genotype accuracies and, consequently, improved genomic predictions. These results suggest that a correction of GBS genotype is necessary, especially for the GBS data with low depths.

SUBMITTER: Wang X

PROVIDER: S-EPMC6350319 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Improving genomic predictions by correction of genotypes from genotyping by sequencing in livestock populations.

Wang Xiao X Lund Mogens Sandø MS Ma Peipei P Janss Luc L Kadarmideen Haja N HN Su Guosheng G

Journal of animal science and biotechnology 20190124

<h4>Background</h4>Genotyping by sequencing (GBS) is a robust method to genotype markers. Many factors can influence the genotyping quality. One is that heterozygous genotypes could be wrongly genotyped as homozygotes, dependent on the genotyping depths. In this study, a method correcting this type of genotyping error was demonstrated. The efficiency of this correction method and its effect on genomic prediction were assessed using simulated data of livestock populations.<h4>Results</h4>Chip arr ...[more]

PMID: 30719286

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Project description:The level of genetic diversity in a population is inversely proportional to the linkage disequilibrium (LD) between individual single nucleotide polymorphisms (SNPs) and quantitative trait loci (QTLs), leading to lower predictive ability of genomic breeding values (GEBVs) in high genetically diverse populations. Haplotype-based predictions could outperform individual SNP predictions by better capturing the LD between SNP and QTL. Therefore, we aimed to evaluate the accuracy and bias of individual-SNP- and haplotype-based genomic predictions under the single-step-genomic best linear unbiased prediction (ssGBLUP) approach in genetically diverse populations. We simulated purebred and composite sheep populations using literature parameters for moderate and low heritability traits. The haplotypes were created based on LD thresholds of 0.1, 0.3, and 0.6. Pseudo-SNPs from unique haplotype alleles were used to create the genomic relationship matrix ( G ) in the ssGBLUP analyses. Alternative scenarios were compared in which the pseudo-SNPs were combined with non-LD clustered SNPs, only pseudo-SNPs, or haplotypes fitted in a second G (two relationship matrices). The GEBV accuracies for the moderate heritability-trait scenarios fitting individual SNPs ranged from 0.41 to 0.55 and with haplotypes from 0.17 to 0.54 in the most (Ne ≅ 450) and less (Ne < 200) genetically diverse populations, respectively, and the bias fitting individual SNPs or haplotypes ranged between -0.14 and -0.08 and from -0.62 to -0.08, respectively. For the low heritability-trait scenarios, the GEBV accuracies fitting individual SNPs ranged from 0.24 to 0.32, and for fitting haplotypes, it ranged from 0.11 to 0.32 in the more (Ne ≅ 250) and less (Ne ≅ 100) genetically diverse populations, respectively, and the bias ranged between -0.36 and -0.32 and from -0.78 to -0.33 fitting individual SNPs or haplotypes, respectively. The lowest accuracies and largest biases were observed fitting only pseudo-SNPs from blocks constructed with an LD threshold of 0.3 (p < 0.05), whereas the best results were obtained using only SNPs or the combination of independent SNPs and pseudo-SNPs in one or two G matrices, in both heritability levels and all populations regardless of the level of genetic diversity. In summary, haplotype-based models did not improve the performance of genomic predictions in genetically diverse populations.

Project description:Enriching of kernel zinc (Zn) concentration in maize is one of the most effective ways to solve the problem of Zn deficiency in low and middle income countries where maize is the major staple food, and 17% of the global population is affected with Zn deficiency. Genomic selection (GS) has shown to be an effective approach to accelerate genetic gains in plant breeding. In the present study, an association-mapping panel and two maize double-haploid (DH) populations, both genotyped with genotyping-by-sequencing (GBS) and repeat amplification sequencing (rAmpSeq) markers, were used to estimate the genomic prediction accuracy of kernel Zn concentration in maize. Results showed that the prediction accuracy of two DH populations was higher than that of the association mapping population using the same set of markers. The prediction accuracy estimated with the GBS markers was significantly higher than that estimated with the rAmpSeq markers in the same population. The maximum prediction accuracy with minimum standard error was observed when half of the genotypes were included in the training set and 3,000 and 500 markers were used for prediction in the association mapping panel and the DH populations, respectively. Appropriate levels of minor allele frequency and missing rate should be considered and selected to achieve good prediction accuracy and reduce the computation burden by balancing the number of markers and marker quality. Training set development with broad phenotypic variation is possible to improve prediction accuracy. The transferability of the GS models across populations was assessed, the prediction accuracies in a few pairwise populations were above or close to 0.20, which indicates the prediction accuracies across years and populations have to be assessed in a larger breeding dataset with closer relationship between the training and prediction sets in further studies. GS outperformed MAS (marker-assisted-selection) on predicting the kernel Zn concentration in maize, the decision of a breeding strategy to implement GS individually or to implement MAS and GS stepwise for improving kernel Zn concentration in maize requires further research. Results of this study provide valuable information for understanding how to implement GS for improving kernel Zn concentration in maize.

Project description:BackgroundThis paper describes a combined heuristic and hidden Markov model (HMM) method to accurately impute missing genotypes in livestock datasets. Genomic selection in breeding programs requires high-density genotyping of many individuals, making algorithms that economically generate this information crucial. There are two common classes of imputation methods, heuristic methods and probabilistic methods, the latter being largely based on hidden Markov models. Heuristic methods are robust, but fail to impute markers in regions where the thresholds of heuristic rules are not met, or the pedigree is inconsistent. Hidden Markov models are probabilistic methods which typically do not require specific family structures or pedigree information, making them very flexible, but they are computationally expensive and, in some cases, less accurate.ResultsWe implemented a new hybrid imputation method that combined heuristic and HMM methods, AlphaImpute and MaCH, and compared the computation time and imputation accuracy of the three methods. AlphaImpute was the fastest, followed by the hybrid method and then the HMM. The computation time of the hybrid method and the HMM increased linearly with the number of iterations used in the hidden Markov model, however, the computation time of the hybrid method increased almost linearly and that of the HMM quadratically with the number of template haplotypes. The hybrid method was the most accurate imputation method for low-density panels when pedigree information was missing, especially if minor allele frequency was also low. The accuracy of the hybrid method and the HMM increased with the number of template haplotypes. The imputation accuracy of all three methods increased with the marker density of the low-density panels. Excluding the pedigree information reduced imputation accuracy for the hybrid method and AlphaImpute. Finally, the imputation accuracy of the three methods decreased with decreasing minor allele frequency.ConclusionsThe hybrid heuristic and probabilistic imputation method is able to impute all markers for all individuals in a population, as the HMM. The hybrid method is usually more accurate and never significantly less accurate than a purely heuristic method or a purely probabilistic method and is faster than a standard probabilistic method.

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Improving genomic predictions by correction of genotypes from genotyping by sequencing in livestock populations.

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Improving genomic predictions by correction of genotypes from genotyping by sequencing in livestock populations.

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