Dataset Information

Genomic prediction based on selected variants from imputed whole-genome sequence data in Australian sheep populations.

ABSTRACT: BACKGROUND:Whole-genome sequence (WGS) data could contain information on genetic variants at or in high linkage disequilibrium with causative mutations that underlie the genetic variation of polygenic traits. Thus far, genomic prediction accuracy has shown limited increase when using such information in dairy cattle studies, in which one or few breeds with limited diversity predominate. The objective of our study was to evaluate the accuracy of genomic prediction in a multi-breed Australian sheep population of relatively less related target individuals, when using information on imputed WGS genotypes. METHODS:Between 9626 and 26,657 animals with phenotypes were available for nine economically important sheep production traits and all had WGS imputed genotypes. About 30% of the data were used to discover predictive single nucleotide polymorphism (SNPs) based on a genome-wide association study (GWAS) and the remaining data were used for training and validation of genomic prediction. Prediction accuracy using selected variants from imputed sequence data was compared to that using a standard array of 50k SNP genotypes, thereby comparing genomic best linear prediction (GBLUP) and Bayesian methods (BayesR/BayesRC). Accuracy of genomic prediction was evaluated in two independent populations that were each lowly related to the training set, one being purebred Merino and the other crossbred Border Leicester x Merino sheep. RESULTS:A substantial improvement in prediction accuracy was observed when selected sequence variants were fitted alongside 50k genotypes as a separate variance component in GBLUP (2GBLUP) or in Bayesian analysis as a separate category of SNPs (BayesRC). From an average accuracy of 0.27 in both validation sets for the 50k array, the average absolute increase in accuracy across traits with 2GBLUP was 0.083 and 0.073 for purebred and crossbred animals, respectively, whereas with BayesRC it was 0.102 and 0.087. The average gain in accuracy was smaller when selected sequence variants were treated in the same category as 50k SNPs. Very little improvement over 50k prediction was observed when using all WGS variants. CONCLUSIONS:Accuracy of genomic prediction in diverse sheep populations increased substantially by using variants selected from whole-genome sequence data based on an independent multi-breed GWAS, when compared to genomic prediction using standard 50K genotypes.

SUBMITTER: Moghaddar N

PROVIDER: S-EPMC6896509 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Genomic prediction based on selected variants from imputed whole-genome sequence data in Australian sheep populations.

Moghaddar Nasir N Khansefid Majid M van der Werf Julius H J JHJ Bolormaa Sunduimijid S Duijvesteijn Naomi N Clark Samuel A SA Swan Andrew A AA Daetwyler Hans D HD MacLeod Iona M IM

Genetics, selection, evolution : GSE 20191205 1

<h4>Background</h4>Whole-genome sequence (WGS) data could contain information on genetic variants at or in high linkage disequilibrium with causative mutations that underlie the genetic variation of polygenic traits. Thus far, genomic prediction accuracy has shown limited increase when using such information in dairy cattle studies, in which one or few breeds with limited diversity predominate. The objective of our study was to evaluate the accuracy of genomic prediction in a multi-breed Austral ...[more]

PMID: 31805849

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Project description:Genomic prediction with imputed whole-genome sequencing (WGS) data is an attractive approach to improve predictive ability with low cost. However, high accuracy has not been realized using this method in livestock. In this study, we imputed 435 individuals from 600K single nucleotide polymorphism (SNP) chip data to WGS data using different reference panels. We also investigated the prediction accuracy of genomic best linear unbiased prediction (GBLUP) using imputed WGS data from different reference panels, linkage disequilibrium (LD)-based marker pruning, and pre-selected variants based on Genome-wide association society (GWAS) results. Results showed that the imputation accuracies from 600K to WGS data were 0.873 ± 0.038, 0.906 ± 0.036, and 0.979 ± 0.010 for the internal, external, and combined reference panels, respectively. In most traits of chickens, the prediction accuracy of imputed WGS data obtained from the internal reference panel was greater than or equal to that of the combined reference panel; the external reference panel had the lowest prediction accuracy. Compared with 600K chip data, GBLUP with imputed WGS data had only a small increase (1-3%) in prediction accuracy. Using only variants selected from imputed WGS data based on GWAS results resulted in almost no increase for most traits and even increased the bias of the regression coefficient. The impact of the degree of LD of selected and remaining variants on prediction accuracy was different. For average daily gain (ADG), residual feed intake (RFI), intestine length (IL), and body weight in 91 days (BW91), the accuracy of GBLUP increased as the degree of LD of selected variants decreased, but the opposite relationship occurred for the remaining variants. But for breast muscle weight (BMW) and average daily feed intake (ADFI), the accuracy of GBLUP increased as the degree of LD of selected variants increased, and the degree of LD of remaining variants had a small effect on prediction accuracy. Overall, the optimal imputation strategy to obtain WGS data for genomic prediction should consider the relationship between selected individuals and target population individuals to avoid heterogeneity of imputation. LD-based marker pruning can be used to improve the accuracy of genomic prediction using imputed WGS data.

Project description:Whole-genome sequence (WGS) data are increasingly being applied into genomic predictions, offering a higher predictive ability by including causal mutations or single-nucleotide polymorphisms (SNPs) putatively in strong linkage disequilibrium with causal mutations affecting the trait. This study aimed to improve the predictive performance of the customized Hanwoo 50 k SNP panel for four carcass traits in commercial Hanwoo population by adding highly predictive variants from sequence data. A total of 16,892 Hanwoo cattle with phenotypes (i.e., backfat thickness, carcass weight, longissimus muscle area, and marbling score), 50 k genotypes, and WGS imputed genotypes were used. We partitioned imputed WGS data according to functional annotation [intergenic (IGR), intron (ITR), regulatory (REG), synonymous (SYN), and non-synonymous (NSY)] to characterize the genomic regions that will deliver higher predictive power for the traits investigated. Animals were assigned into two groups, the discovery set (7324 animals) used for predictive variant detection and the cross-validation set for genomic prediction. Genome-wide association studies were performed by trait to every genomic region and entire WGS data for the pre-selection of variants. Each set of pre-selected SNPs with different density (1000, 3000, 5000, or 10,000) were added to the 50 k genotypes separately and the predictive performance of each set of genotypes was assessed using the genomic best linear unbiased prediction (GBLUP). Results showed that the predictive performance of the customized Hanwoo 50 k SNP panel can be improved by the addition of pre-selected variants from the WGS data, particularly 3000 variants from each trait, which is then sufficient to improve the prediction accuracy for all traits. When 12,000 pre-selected variants (3000 variants from each trait) were added to the 50 k genotypes, the prediction accuracies increased by 9.9, 9.2, 6.4, and 4.7% for backfat thickness, carcass weight, longissimus muscle area, and marbling score compared to the regular 50 k SNP panel, respectively. In terms of prediction bias, regression coefficients for all sets of genotypes in all traits were close to 1, indicating an unbiased prediction. The strategy used to select variants based on functional annotation did not show a clear advantage compared to using whole-genome. Nonetheless, such pre-selected SNPs from the IGR region gave the highest improvement in prediction accuracy among genomic regions and the values were close to those obtained using the WGS data for all traits. We concluded that additional gain in prediction accuracy when using pre-selected variants appears to be trait-dependent, and using WGS data remained more accurate compared to using a specific genomic region.

Project description:BackgroundWhole-genome sequence (WGS) data harbor causative variants that may not be present in standard single nucleotide polymorphism (SNP) chip data. The objective of this study was to investigate the impact of using preselected variants from WGS for single-step genomic predictions in maternal and terminal pig lines with up to 1.8k sequenced and 104k sequence imputed animals per line.MethodsTwo maternal and four terminal lines were investigated for eight and seven traits, respectively. The number of sequenced animals ranged from 1365 to 1491 for the maternal lines and 381 to 1865 for the terminal lines. Imputation to sequence occurred within each line for 66k to 76k animals for the maternal lines and 29k to 104k animals for the terminal lines. Two preselected SNP sets were generated based on a genome-wide association study (GWAS). Top40k included the SNPs with the lowest p-value in each of the 40k genomic windows, and ChipPlusSign included significant variants integrated into the porcine SNP chip used for routine genotyping. We compared the performance of single-step genomic predictions between using preselected SNP sets assuming equal or different variances and the standard porcine SNP chip.ResultsIn the maternal lines, ChipPlusSign and Top40k showed an average increase in accuracy of 0.6 and 4.9%, respectively, compared to the regular porcine SNP chip. The greatest increase was obtained with Top40k, particularly for fertility traits, for which the initial accuracy based on the standard SNP chip was low. However, in the terminal lines, Top40k resulted in an average loss of accuracy of 1%. ChipPlusSign provided a positive, although small, gain in accuracy (0.9%). Assigning different variances for the SNPs slightly improved accuracies when using variances obtained from BayesR. However, increases were inconsistent across the lines and traits.ConclusionsThe benefit of using sequence data depends on the line, the size of the genotyped population, and how the WGS variants are preselected. When WGS data are available on hundreds of thousands of animals, using sequence data presents an advantage but this remains limited in pigs.

Project description:BackgroundSouth Africa and Australia shares multiple important sheep breeds. For some of these breeds, genomic breeding values are provided to breeders in Australia, but not yet in South Africa. Combining genomic resources could facilitate development for across country selection, but the influence of population structures could be important to the compatability of genomic data from varying origins. The genetic structure within and across breeds, countries and strains was evaluated in this study by population genomic parameters derived from SNP-marker data. Populations were first analysed by breed and country of origin and then by subpopulations of South African and Australian Merinos.ResultsMean estimated relatedness according to the genomic relationship matrix varied by breed (-0.11 to 0.16) and bloodline (-0.08 to 0.06) groups and depended on co-ancestry as well as recent genetic links. Measures of divergence across bloodlines (FST: 0.04-0.12) were sometimes more distant than across some breeds (FST: 0.05-0.24), but the divergence of common breeds from their across-country equivalents was weak (FST: 0.01-0.04). According to mean relatedness, FST, PCA and Admixture, the Australian Ultrafine line was better connected to the SA Cradock Fine Wool flock than with other AUS bloodlines. Levels of linkage disequilibrium (LD) between adjacent markers was generally low, but also varied across breeds (r2: 0.14-0.22) as well as bloodlines (r2: 0.15-0.19). Patterns of LD decay was also unique to breeds, but bloodlines differed only at the absolute level. Estimates of effective population size (Ne) showed genetic diversity to be high for the majority of breeds (Ne: 128-418) but also for bloodlines (Ne: 137-369).ConclusionsThis study reinforced the genetic complexity and diversity of important sheep breeds, especially the Merino breed. The results also showed that implications of isolation can be highly variable and extended beyond breed structures. However, knowledge of useful links across these population substructures allows for a fine-tuned approach in the combination of genomic resources. Isolation across country rarely proved restricting compared to other structures considered. Consequently, research into the accuracy of across-country genomic prediction is recommended.

Dataset Information

Genomic prediction based on selected variants from imputed whole-genome sequence data in Australian sheep populations.

Publications

Genomic prediction based on selected variants from imputed whole-genome sequence data in Australian sheep populations.

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