Nasir Moghaddar

Multiple-trait QTL mapping and genomic prediction for wool traits in sheep

BackgroundThe application of genomic selection to sheep breeding could lead to substantial increases in profitability of wool production due to the availability of accurate breeding values from single nucleotide polymorphism (SNP) data. Several key traits determine the value of wool and influence a sheep’s susceptibility to fleece rot and fly strike. Our aim was to predict genomic estimated breeding values (GEBV) and to compare three methods of combining information across traits to map polymorphisms that affect these traits.MethodsGEBV for 5726 Merino and Merino crossbred sheep were calculated using BayesR and genomic best linear unbiased prediction (GBLUP) with real and imputed 510,174 SNPs for 22 traits (at yearling and adult ages) including wool production and quality, and breech conformation traits that are associated with susceptibility to fly strike. Accuracies of these GEBV were assessed using fivefold cross-validation. We also devised and compared three approximate multi-trait analyses to map pleiotropic quantitative trait loci (QTL): a multi-trait genome-wide association study and two multi-trait methods that use the output from BayesR analyses. One BayesR method used local GEBV for each trait, while the other used the posterior probabilities that a SNP had an effect on each trait.ResultsBayesR and GBLUP resulted in similar average GEBV accuracies across traits (~0.22). BayesR accuracies were highest for wool yield and fibre diameter (>0.40) and lowest for skin quality and dag score (<0.10). Generally, accuracy was higher for traits with larger reference populations and higher heritability. In total, the three multi-trait analyses identified 206 putative QTL, of which 20 were common to the three analyses. The two BayesR multi-trait approaches mapped QTL in a more defined manner than the multi-trait GWAS. We identified genes with known effects on hair growth (i.e. FGF5, STAT3, KRT86, and ALX4) near SNPs with pleiotropic effects on wool traits.ConclusionsThe mean accuracy of genomic prediction across wool traits was around 0.22. The three multi-trait analyses identified 206 putative QTL across the ovine genome. Detailed phenotypic information helped to identify likely candidate genes.

Genomic prediction of weight and wool traits in a multi-breed sheep population

The objective of this study was to predict the accuracy of genomic prediction for 26 traits, including weight, muscle, fat, and wool quantity and quality traits, in Australian sheep based on a large, multi-breed reference population. The reference population consisted of two research flocks, with the main breeds being Merino, Border Leicester (BL), Poll Dorset (PD), and White Suffolk (WS). The genomic estimated breeding value (GEBV) was based on GBLUP (genomic best linear unbiased prediction), applying a genomic relationship matrix calculated from the 50K Ovine SNP chip marker genotypes. The accuracy of GEBV was evaluated as the Pearson correlation coefficient between GEBV and accurate estimated breeding value based on progeny records in a set of genotyped industry animals. The accuracies of weight traits were relatively low to moderate in PD and WS breeds (0.11–0.27) and moderate to relatively high in BL and Merino (0.25–0.63). The accuracy of muscle and fat traits was moderate to relatively high across all breeds (between 0.21 and 0.55). The accuracy of GEBV of yearling and adult wool traits in Merino was, on average, high (0.33–0.75). The results showed the accuracy of genomic prediction depends on trait heritability and the effective size of the reference population, whereas the observed GEBV accuracies were more related to the breed proportions in the multi-breed reference population. No extra gain in within-breed GEBV accuracy was observed based on across breed information. More investigations are required to determine the precise effect of across-breed information on within-breed genomic prediction.

Genomic prediction from observed and imputed high-density ovine genotypes

Background Genomic prediction using high-density (HD) marker genotypes is expected to lead to higher prediction accuracy, particularly for more heterogeneous multi-breed and crossbred populations such as those in sheep and beef cattle, due to providing stronger linkage disequilibrium between single nucleotide polymorphisms and quantitative trait loci controlling a trait. The objective of this study was to evaluate a possible improvement in genomic prediction accuracy of production traits in Australian sheep breeds based on HD genotypes (600k, both observed and imputed) compared to prediction based on 50k marker genotypes. In particular, we compared improvement in prediction accuracy of animals that are more distantly related to the reference population and across sheep breeds.MethodsGenomic best linear unbiased prediction (GBLUP) and a Bayesian approach (BayesR) were used as prediction methods using whole or subsets of a large multi-breed/crossbred sheep reference set. Empirical prediction accuracy was evaluated for purebred Merino, Border Leicester, Poll Dorset and White Suffolk sire breeds according to the Pearson correlation coefficient between genomic estimated breeding values and breeding values estimated based on a progeny test in a separate dataset.ResultsResults showed a small absolute improvement (0.0 to 8.0% and on average 2.2% across all traits) in prediction accuracy of purebred animals from HD genotypes when prediction was based on the whole dataset. Greater improvement in prediction accuracy (1.0 to 12.0% and on average 5.2%) was observed for animals that were genetically lowly related to the reference set while it ranged from 0.0 to 5.0% for across-breed prediction. On average, no significant advantage was observed with BayesR compared to GBLUP.

Effect of selection on bias and accuracy in genomic prediction of breeding values

Reference populations for genomic selection (GS) usually involve highly selected individuals, which may result in biased prediction of estimated genomic breeding values (GEBV). In the present study, bias and accuracy of GEBV were explored for various genetic models and prediction methods when using selected individuals for a reference. Data were simulated for an animal breeding program to compare Best Linear Unbiased Prediction of breeding values using pedigree based relationships (PBLUP), genomic relationships for genotyped animals only (GBLUP) and a Single Step approach (SSGBLUP), where information on genotyped individuals was used to infer a matrix H with relationships among all available genotyped and non-genotyped individuals that were linked through pedigree. In SSGBLUP, various weights (α=0.95, 0.80, 0.50) for the genomic relationship matrix (G) relative to the numerator relationship matrix (A) were applied to construct H and in another version (SSGBLUP_F), inbreeding was accounted for while computing A-1. With GBLUP, accuracy of GEBV prediction increased linearly with an increase in the number of animals selected in reference. For the scenario with no-selection and random mating (RR) prediction was unbiased. For GBLUP, lower accuracy and bias observed in the scenarios with selection and random mating (SR) or selection and positive assortative mating (SA), in which prediction bias increased when a smaller and highly selected proportion genotyped. Bias disappeared when all individuals were genotyped. SSGBLUP_F showed higher accuracy compared to GBLUP and bias of prediction was negligible even with selective genotyping. However, PBLUP and SSGBLUP showed bias in SA owing to not fully accounting for allele frequency changes because of selection of quantitative trait loci (QTL) with larger effects and also due to high inbreeding rate. In genetic models with fewer QTL but each with larger effect, predictions were less accurate and more biased for selection scenarios. Results suggest that prediction accuracy and bias is affected by the genetic architecture of the trait. Selective genotyping lead to significant bias in GEBV prediction. SSGBLUP with appropriate scaling of A and G matrices can provide accurate and less biased prediction but scaling requires careful consideration in populations under selection and with high levels of inbreeding.

Genotype × birth type or rearing-type interactions for growth and ultrasound scanning traits in Merino sheep

This study explores the interaction between genetic potential for growth in Merino lambs and their birth type (BT) or rearing type (RT). Data on birthweight (BWT), weaning weight (WWT), post-weaning weight (PWWT), scan fat (PFAT) and eye muscle depth (PEMD) were used from 3920 single and 4492 twin-born lambs from 285 sires and 5279 dams. Univariate analysis showed a significant sire × BT interaction accounting for 1.59% and 2.49% of the phenotypic variation for BWT and WWT, respectively, and no significant effect for PWWT, PFAT and PEMD. Sire × RT interaction effects were much smaller and only significant for PEMD. Bivariate analysis indicated that the genetic correlation (rg) between trait expression in lambs born and reared as singles versus those born and reared as twins were high for BWT, WWT, PWWT (0.91 ± 0.02 – 0.96 ± 0.01), whereas rg for PFAT and PEMD were lower (0.81 ± 0.03 and 0.86 ± 0.02). The rg between traits expressed in lambs born and reared as singles versus those born as twins but reared as singles were lower: 0.77 ± 0.08, 0.88 ± 0.03, 0.66 ± 0.06 and 0.61 ± 0.08 for WWT, PWWT, PFAT and PEMD, respectively. A different RT only affected the expression of breeding values for PFAT and PEMD (rg 0.62 ± 0.04 and 0.47 ± 0.03, respectively). This study showed genotype × environment interaction for BWT and WWT (sire × BT interaction) and for PEMD (sire by RT interaction). However, sires’ breeding value of a model that accounts for sire × BT interaction provides a very similar ranking of sires compared with a model that ignores it, implying that there is no need to correct for the effect in models for genetic evaluation.