Accuracy of genomic prediction of shell quality in a White Leghorn line.

Several genomic methods were applied for predicting shell quality traits recorded at 4 different hen ages in a White Leghorn line. The accuracies of genomic prediction of single-step GBLUP and single-trait Bayes B were compared with predictions of breeding values based on pedigree-BLUP under single-trait or multitrait models. Breaking strength (BS) and dynamic stiffness (Kdyn) measurements were collected on 18,524 birds from 3 consecutive generations, of which 4,164 animals also had genotypes from an Affymetrix 50K panel containing 49,591 SNPs after quality control edits. All traits had low to moderate heritability, ranging from 0.17 for BS to 0.34 for Kdyn. The highest accuracies of prediction were obtained for the multitrait single-step model. The use of marker information resulted in higher prediction accuracies than pedigree-based models for almost all traits. A genome-wide association study based on a Bayes B model was conducted to detect regions explaining the largest proportion of genetic variance. Across all 8 shell quality traits analyzed, 7 regions each explaining over 2% of genetic variance and 54 regions each explaining over 1% of genetic variance were identified. The windows explaining a large proportion of genetic variance overlapped with several potential candidate genes with biological functions linked to shell formation. A multitrait repeatability model using a single-step method is recommended for genomic evaluation of shell quality in layer chickens.

A comparison of identity-by-descent and identity-by-state matrices that are used for genetic evaluation and estimation of variance components.

The genetic covariance matrix conditional on pedigree is proportional to the pedigree-based additive relationship matrix (PARM), which is twice the matrix of identity-by-descent (IBD) probabilities. In genomic prediction, IBD probabilities in the PARM, which are expected genetic similarities between relatives that are derived from the pedigree, are substituted by realized similarities that are derived from genotypes to obtain a genomic additive relationship matrix (GARM). Different definitions of similarity lead to different GARMs, and two commonly used GARMS are the matrix G, which is based on an allele substitution effect model, and the matrix T, which is based on an allele effect model. We show that although the two matrices T and G are not proportional, they give identical predictions of differences between breeding values. When genomic information is used for variance component estimation, the GARM Gx is computed from genotype covariates that have been standardized to have unit variance. That approach is equivalent to fitting a random regression model using the same standardized covariates. We show that under Hardy-Weinberg and linkage equilibria (LE) that the genetic variance is kσγ2, where σγ2 is the variance of a randomly sampled element from the vector of k substitution effects. However, if linkage disequilibrium (LD) has been generated through selection, covariances between genotypes at different loci will be negative, and therefore, the additive genetic variance will be lower than kσγ2. When the GARM Gx is assumed to be proportional to the genetic covariance matrix, the parameter being estimated is kσγ2. We have demonstrated by simulation that kσγ2 overestimates the additive genetic variance when LD is generated by selection. We argue that unlike the PARM, GARMs are not proportional to a genetic covariance matrix conditional on the observed causal genotypes. The objective here is to recognize the difference between these covariance matrices and its implications.

Epistatic interactions associated with fatty acid concentrations of beef from angus sired beef cattle.

BACKGROUND: Consumers are becoming increasingly conscientious about the nutritional value of their food. Consumption of some fatty acids has been associated with human health traits such as blood pressure and cardiovascular disease. Therefore, it is important to investigate genetic variation in content of fatty acids present in meat. Previously publications reported regions of the cattle genome that are additively associated with variation in fatty acid content. This study evaluated epistatic interactions, which could account for additional genetic variation in fatty acid content. RESULTS: Epistatic interactions for 44 fatty acid traits in a population of Angus beef cattle were evaluated with EpiSNPmpi. False discovery rate (FDR) was controlled at 5 % and was limited to well-represented genotypic combinations. Epistatic interactions were detected for 37 triacylglyceride (TAG), 36 phospholipid (PL) fatty acid traits, and three weight traits. A total of 6,181, 7,168, and 0 significant epistatic interactions (FDR < 0.05, 50-animals per genotype combination) were associated with Triacylglyceride fatty acids, Phospholipid fatty acids, and weight traits respectively and most were additive-by-additive interactions. A large number of interactions occurred in potential regions of regulatory control along the chromosomes where genes related to fatty acid metabolism reside. CONCLUSIONS: Many fatty acids were associated with epistatic interactions. Despite a large number of significant interactions, there are a limited number of genomic locations that harbored these interactions. While larger population sizes are needed to accurately validate and quantify these epistatic interactions, the current findings point towards additional genetic variance that can be accounted for within these fatty acid traits.

Genetic relationship between purebred and crossbred sow longevity.

BACKGROUND: The overall breeding objective for a nucleus swine selection program is to improve crossbred commercial performance. Most genetic improvement programs are based on an assumed high degree of positive relationship between purebred performance in a nucleus herd and their relatives' crossbred performance in a commercial herd. The objective of this study was to examine the relationship between purebred and crossbred sow longevity performance. Sow longevity was defined as a binary trait with a success occurring if a sow remained in the herd for a certain number of parities and including the cumulative number born alive as a measure of reproductive success. Heritabilities, genetic correlations, and phenotypic correlations were estimated using THRGIBBS1F90. RESULTS: Results indicated little to no genetic correlations between crossbred and purebred reproductive traits. This indicates that selection for longevity or lifetime performance at the nucleus level may not result in improved longevity and lifetime performance at the crossbred level. Early parity performance was highly correlated with lifetime performance indicating that an indicator trait at an early parity could be used to predict lifetime performance. This would allow a sow to have her own record for the selection trait before she has been removed from the herd. CONCLUSIONS: Results from this study aid in quantifying the relationship between purebred and crossbred performance and provide information for genetic companies to consider when developing a selection program where the objective is to improve crossbred sow performance. Utilizing crossbred records in a selection program would be the best way to improve crossbred sow productivity.

Impact of fitting dominance and additive effects on accuracy of genomic prediction of breeding values in layers.

Most genomic prediction studies fit only additive effects in models to estimate genomic breeding values (GEBV). However, if dominance genetic effects are an important source of variation for complex traits, accounting for them may improve the accuracy of GEBV. We investigated the effect of fitting dominance and additive effects on the accuracy of GEBV for eight egg production and quality traits in a purebred line of brown layers using pedigree or genomic information (42K single-nucleotide polymorphism (SNP) panel). Phenotypes were corrected for the effect of hatch date. Additive and dominance genetic variances were estimated using genomic-based [genomic best linear unbiased prediction (GBLUP)-REML and BayesC] and pedigree-based (PBLUP-REML) methods. Breeding values were predicted using a model that included both additive and dominance effects and a model that included only additive effects. The reference population consisted of approximately 1800 animals hatched between 2004 and 2009, while approximately 300 young animals hatched in 2010 were used for validation. Accuracy of prediction was computed as the correlation between phenotypes and estimated breeding values of the validation animals divided by the square root of the estimate of heritability in the whole population. The proportion of dominance variance to total phenotypic variance ranged from 0.03 to 0.22 with PBLUP-REML across traits, from 0 to 0.03 with GBLUP-REML and from 0.01 to 0.05 with BayesC. Accuracies of GEBV ranged from 0.28 to 0.60 across traits. Inclusion of dominance effects did not improve the accuracy of GEBV, and differences in their accuracies between genomic-based methods were small (0.01-0.05), with GBLUP-REML yielding higher prediction accuracies than BayesC for egg production, egg colour and yolk weight, while BayesC yielded higher accuracies than GBLUP-REML for the other traits. In conclusion, fitting dominance effects did not impact accuracy of genomic prediction of breeding values in this population.

Use of robust multivariate linear mixed models for estimation of genetic parameters for carcass traits in beef cattle.

Assumptions of normality of residuals for carcass evaluation may make inferences vulnerable to the presence of outliers, but heavy-tail densities are viable alternatives to normal distributions and provide robustness against unusual or outlying observations when used to model the densities of residual effects. We compare estimates of genetic parameters by fitting multivariate Normal (MN) or heavy-tail distributions (multivariate Student's t and multivariate Slash, MSt and MS) for residuals in data of hot carcass weight (HCW), longissimus muscle area (REA) and 12th to 13th rib fat (FAT) traits in beef cattle using 2475 records from 2007 to 2008 from a large commercial operation in Nebraska. Model comparisons using deviance information criteria (DIC) favoured MSt over MS and MN models, respectively. The posterior means (and 95% posterior probability intervals, PPI) of v for the MSt and MS models were 5.89 ± 0.90 (4.35, 7.86) and 2.04 ± 0.18 (1.70, 2.41), respectively. Smaller values of posterior densities of v for MSt and MS models confirm that the assumption of normally distributed residuals is not adequate for the analysis of the data set. Posterior mean (PM) and posterior median (PD) estimates of direct genetic variances were variable with MSt having the highest mean value followed by MS and MN, respectively. Posterior inferences on genetic variance were, however, comparable among the models for FAT. Posterior inference on additive heritabilities for HCW, REA and FAT using MN, MSt and MS models indicated similar and moderate heritability comparable with the literature. Posterior means of genetic correlations for carcass traits were variable but positive except for between REA and FAT, which showed an antagonistic relationship. We have demonstrated that genetic evaluation and selection strategies will be sensitive to the assumed model for residuals.

Genome-wide association study for egg production and quality in layer chickens.

Discovery of genes with large effects on economically important traits has for many years been of interest to breeders. The development of SNP panels which cover the whole genome with high density and, more importantly, that can be genotyped on large numbers of individuals at relatively low cost, has opened new opportunities for genome-wide association studies (GWAS). The objective of this study was to find genomic regions associated with egg production and quality traits in layers using analysis methods developed for the purpose of whole genome prediction. Genotypes on over 4500 birds and phenotypes on over 13,000 hens from eight generations of a brown egg layer line were used. Birds were genotyped with a custom 42K Illumina SNP chip. Recorded traits included two egg production and 11 egg quality traits (puncture score, albumen height, yolk weight and shell colour) at early and late stages of production, as well as body weight and age at first egg. Egg weight was previously analysed by Wolc et al. (2012). The Bayesian whole genome prediction model--BayesB (Meuwissen et al. 2001) was used to locate 1 Mb regions that were most strongly associated with each trait. The posterior probability of a 1 Mb window contributing to genetic variation was used as the criterion for suggesting the presence of a quantitative trait locus (QTL) in that window. Depending upon the trait, from 1 to 7 significant (posterior probability >0.9) 1 Mb regions were found. The largest QTL, a region explaining 32% of genetic variance, was found on chr4 at 78 Mb for body weight but had pleiotropic effects on other traits. For the other traits, the largest effects were much smaller, explaining <7% of genetic variance, with regions on chromosomes 2, 12 and 17 explaining above 5% of genetic variance for albumen height, shell colour and egg production, respectively. In total, 45 of 1043 1 Mb windows were estimated to have a non-zero effect with posterior probability > 0.9 for one or more traits.

Accuracy of genomic prediction using an evenly spaced, low-density single nucleotide polymorphism panel in broiler chickens.

One approach for cost-effective implementation of genomic selection is to genotype training individuals with a high-density (HD) panel and selection candidates with an evenly spaced, low-density (ELD) panel. The purpose of this study was to evaluate the extent to which the ELD approach reduces the accuracy of genomic estimated breeding values (GEBV) in a broiler line, in which 1,091 breeders from 3 generations were used for training and 160 progeny of the third generation for validation. All birds were genotyped with an Illumina Infinium platform HD panel that included 20,541 segregating markers. Two subsets of HD markers, with 377 (ELD-1) or 766 (ELD-2) markers, were selected as ELD panels. The ELD-1 panel was genotyped using KBiosciences KASPar SNP genotyping chemistry, whereas the ELD-2 panel was simulated by adding markers from the HD panel to the ELD-1 panel. The training data set was used for 2 traits: BW at 35 d on both sexes and hen house production (HHP) between wk 28 and 54. Methods Bayes-A, -B, -C and genomic best linear unbiased prediction were used to estimate HD-marker effects. Two scenarios were used: (1) the 160 progeny were ELD-genotyped, and (2) the 160 progeny and their dams (117 birds) were ELD-genotyped. The missing HD genotypes in ELD-genotyped birds were imputed by a Gibbs sampler, capitalizing on linkage within families. In scenario (1), the correlation of GEBV for BW (HHP) of the 160 progeny based on observed HD versus imputed genotypes was greater than 0.94 (0.98) with the ELD-1 panel and greater than 0.97 (0.99) with the ELD-2 panel. In scenario (2), the correlation of GEBV for BW (HHP) was greater than 0.92 (0.96) with the ELD-1 panel and greater than 0.95 (0.98) with the ELD-2 panel. Hence, in a pedigreed population, genomic selection can be implemented by genotyping selection candidates with about 400 ELD markers with less than 6% loss in accuracy. This leads to substantial savings in genotyping costs, with little sacrifice in accuracy.

Application of multivariate heavy-tailed distributions to residuals in the estimation of genetic parameters of growth traits in beef cattle.

Assumptions of normality in most animal breeding applications may make inferences vulnerable to the presence of outliers. Heavy-tail densities are viable alternatives to normal distributions and provide robustness against unusual or outlying observations when used to model the densities of residual effects. Our objective is to compare estimates of genetic parameters by fitting multivariate normal (MN) or heavy-tail distributions [multivariate Student's t (MSt) and multivariate slash (MS)] for residuals in data of body birth weight (BBW), weaning (WW), and yearling (YW) weight traits in beef cattle. A total of 17,019 weight records for BBW, WW, and YW from 1998 through 2010 from a large commercial cow/calf operation in the sand hills of Nebraska were analyzed. Models included fixed effects of contemporary group and sire breed whereas animal and maternal effects were random and the degrees of freedom (v) was treated as unknown for MSt and MS. Model comparisons using deviance information criteria (DIC) favored MSt over MS and MN models, respectively. The posterior means [and 95% posterior probability intervals (PPI)] of v for the MSt and MS models were 5.28 (4.80, 5.85) and 1.88 (1.76, 2.00), respectively. Smaller values of posterior densities of v for MSt and MS models confirm that the assumption of normally distributed residuals is not adequate for the analysis of BBW, WW, and YW datasets. Posterior mean (PM) and posterior median (PD) estimates of direct and maternal genetic variances were the same and posterior densities of these parameters were found to be symmetric. The 95% PPI estimates from MN and MSt models for BBW did not overlap, which indicates significant difference between PM estimates from MN or MSt models. The observed antagonistic relationship between additive direct and additive maternal effects indicated that genetic evaluation and selection strategies will be sensitive to the assumed model for residuals.

Heritability and Bayesian genome-wide association study of first service conception and pregnancy in Brangus heifers.

Brangus [3/8 Brahman (Bos indicus) × 5/8 Angus (Bos taurus); n ≈ 800] heifers from 67 sires were used to estimate heritability and conduct a genome-wide association study (GWAS) for 2 binary fertility traits: first service conception (FSC) and heifer pregnancy (HPG). Genotypes were from 53,692 loci on the BovineSNP50 (Infinium Bead Chips, Illumina, San Diego, CA). Yearling heifers were estrous synchronized, bred by AI, and then exposed to natural service breeding. Reproductive ultrasound and DNA-based parentage testing were used to determine if the heifer conceived by AI or natural service, and code for FSC and HPG traits. Success rates for FSC and HPG were 53.3% and 78.0% ± 0.01%, and corresponding heritability estimates were 0.18 ± 0.07 and 0.10 ± 0.06, respectively. The models used in obtaining these heritability estimates and GWAS included fixed effects of year (i.e., 2005 to 2007), birth location, calving season, age of dam, and contemporary group. In GWAS, simultaneous associations of 1 Mb SNP windows with phenotype were undertaken with Bayes C analyses using GenSel software. The 1 Mb windows contained 21.3 ± 1.1 SNP. Analyses fitted a mixture model that treated SNP effects as random, with an assumed fraction pi = 0.9995 having no effect on phenotype. The windows that accounted for 1.0% of genetic variance were considered as QTL associated with FSC or HPG. Eighteen QTL existed on 15 chromosomes for the 2 traits. On average, each QTL accounted for 2.43% ± 0.2% of the genetic variance. Chromosome 8 harbored 2 QTL for FSC and 1 for HPG; however, these regions did not overlap. Chromosomes 3, 15, 16, 19, 24, 26, 27, 29, and X included QTL only for FSC, whereas chromosomes 2, 4, 10, 13, and 20 contained QTL only for HPG. The multitude of QTL detected for FSC and HPG in this GWAS involving Brangus heifers exemplifies the complex regulation of variation in heifer fertility traits of low heritability.

Bayesian genome-wide association analysis of growth and yearling ultrasound measures of carcass traits in Brangus heifers.

Data from developing Brangus heifers (3/8 Brahman-Bos indicus × 5/8 Angus-Bos taurus; n ≈ 802 from 67 sires) registered with International Brangus Breeders Association were analyzed to detect QTL associated with growth traits and ultrasound measures of carcass traits. Genotypes were from BovineSNP50 (Infinium BeadChip, Illumina, San Diego, CA; 53,692 SNP). Phenotypes included BW collected at birth and ∼205 and 365 d of age, and yearling ultrasound assessment of LM area, percent intramuscular fat, and depth of rib fat. Simultaneous association of SNP windows with phenotype were undertaken with Bayes C analyses, using GenSel software. The SNP windows were ≈ 5 SNP in length. Analyses fitted a mixture model that treated SNP effects as random, with an assumed fraction pi = 0.999 having no effect on phenotype. Bootstrap analyses were used to obtain significance values for the SNP windows with the greatest contribution to observed variation. The SNP windows with P < 0.01 were considered as QTL associated with a trait in which case their location was queried from dbSNP and the presence of a previously reported QTL in that location was checked in CattleQTLdb. For 9 traits, QTL were mapped to 139 regions on 25 chromosomes. Forty-one of these QTL were already described in CattleQTLdb, so 98 are new additions. The SNP windows on chromosomes 1, 3, and 6 were associated with multiple traits (i.e., 205- and 365- d BW, and ADG from birth to 205 and 365 d of age). Several chromosomes harbored regions associated with multiple traits; however, the SNP that comprised the window often varied among traits (i.e., chromosomes 1, 3, 4, 5, 6, 7, 9, 10, 11, 13, 14, 15, 16, 20, 21, 22, 24, 28, and 29). Results from whole genome association of SNP with growth and ultrasound carcass traits in developing Brangus heifers confirmed several published QTL and detected several new QTL.

Accuracy of genomic selection methods in a standard data set of loblolly pine (Pinus taeda L.).

Genomic selection can increase genetic gain per generation through early selection. Genomic selection is expected to be particularly valuable for traits that are costly to phenotype and expressed late in the life cycle of long-lived species. Alternative approaches to genomic selection prediction models may perform differently for traits with distinct genetic properties. Here the performance of four different original methods of genomic selection that differ with respect to assumptions regarding distribution of marker effects, including (i) ridge regression-best linear unbiased prediction (RR-BLUP), (ii) Bayes A, (iii) Bayes Cπ, and (iv) Bayesian LASSO are presented. In addition, a modified RR-BLUP (RR-BLUP B) that utilizes a selected subset of markers was evaluated. The accuracy of these methods was compared across 17 traits with distinct heritabilities and genetic architectures, including growth, development, and disease-resistance properties, measured in a Pinus taeda (loblolly pine) training population of 951 individuals genotyped with 4853 SNPs. The predictive ability of the methods was evaluated using a 10-fold, cross-validation approach, and differed only marginally for most method/trait combinations. Interestingly, for fusiform rust disease-resistance traits, Bayes Cπ, Bayes A, and RR-BLUB B had higher predictive ability than RR-BLUP and Bayesian LASSO. Fusiform rust is controlled by few genes of large effect. A limitation of RR-BLUP is the assumption of equal contribution of all markers to the observed variation. However, RR-BLUP B performed equally well as the Bayesian approaches.The genotypic and phenotypic data used in this study are publically available for comparative analysis of genomic selection prediction models.

A two-stage approximation for analysis of mixture genetic models in large pedigrees.

Information from cosegregation of marker and QTL alleles, in addition to linkage disequilibrium (LD), can improve genomic selection. Variance components linear models have been proposed for this purpose, but accommodating dominance and epistasis is not straightforward with them. A full-Bayesian analysis of a mixture genetic model is favorable in this respect, but is computationally infeasible for whole-genome analyses. Thus, we propose an approximate two-step approach that neglects information from trait phenotypes in inferring ordered genotypes and segregation indicators of markers. Quantitative trait loci (QTL) fine-mapping scenarios, using high-density markers and pedigrees of five generations without genotyped females, were simulated to test this strategy against an exact full-Bayesian approach. The latter performed better in estimating QTL genotypes, but precision of QTL location and accuracy of genomic breeding values (GEBVs) did not differ for the two methods at realistically low LD. If, however, LD was higher, the exact approach resulted in a slightly higher accuracy of GEBVs. In conclusion, the two-step approach makes mixture genetic models computationally feasible for high-density markers and large pedigrees. Furthermore, markers need to be sampled only once and results can be used for the analysis of all traits. Further research is needed to evaluate the two-step approach for complex pedigrees and to analyze alternative strategies for modeling LD between QTL and markers.

Genomic prediction of simulated multibreed and purebred performance using observed fifty thousand single nucleotide polymorphism genotypes.

Genomic prediction involves characterization of chromosome fragments in a training population to predict merit. Confidence in the predictions relies on their evaluation in a validation population. Many commercial animals are multibreed (MB) or crossbred, but seedstock populations tend to be purebred (PB). Training in MB allows selection of PB for crossbred performance. Training in PB to predict MB performance quantifies the potential for across-breed genomic prediction. Efficiency of genomic selection was evaluated for a trait with heritability 0.5 simulated using actual SNP genotypes. The PB population had 1,086 Angus animals, and the MB population had 924 individuals from 8 sire breeds. Phenotypic values were simulated for scenarios including 50, 100, 250, or 500 additive QTL randomly selected from 50K SNP panels. Panels containing various numbers of SNP, including or excluding the QTL, were used in the analysis. A Bayesian model averaging method was used to simultaneously estimate the effects of all markers on the panels in MB (or PB) training populations. Estimated effects were utilized to predict genomic merit of animals in PB (or MB) validation populations. Correlations between predicted and simulated genomic merit in the validation population was used to reflect predictive ability. Panels that included QTL were able to account for 50% or more of the within-breed genetic variance when the trait was influenced by 50 QTL. The predictive power eroded as the number of QTL increased. Panels that composed the QTL and no other markers were able to account for 50% or more genetic variance even with 500 QTL. Panels that included genomic markers as well as QTL had less predictive power as the number of markers on the panel was increased. Panels that excluded the QTL and relied on markers in linkage disequilibrium (LD) to predict QTL effects performed more poorly than marker panels with QTL. Real-life situations with 50K panels that excluded the QTL could account for no more than 20% genetic variation for 50 QTL and less than 10% for 500 QTL. The difference between panels that included and excluded QTL indicates that the predictive ability of existing panels is limited by their LD. Training in PB to predict MB tended to be more predictive than training in MB to predict PB due to greater average levels of LD in PB than in MB populations. Improved across breed prediction of genomic merit will require panels with more than 50,000 markers.

Genomic selection in admixed and crossbred populations.

In livestock, genomic selection (GS) has primarily been investigated by simulation of purebred populations. Traits of interest are, however, often measured in crossbred or mixed populations with uncertain breed composition. If such data are used as the training data for GS without accounting for breed composition, estimates of marker effects may be biased due to population stratification and admixture. To investigate this, a genome of 100 cM was simulated with varying marker densities (5 to 40 segregating markers per cM). After 1,000 generations of random mating in a population of effective size 500, 4 lines with effective size 100 were isolated and mated for another 50 generations to create 4 pure breeds. These breeds were used to generate combined, F(1), F(2), 3- and 4-way crosses, and admixed training data sets of 1,000 individuals with phenotypes for an additive trait controlled by 100 segregating QTL and heritability of 0.30. The validation data set was a sample of 1,000 genotyped individuals from one pure breed. Method Bayes-B was used to simultaneously estimate the effects of all markers for breeding value estimation. With 5 (40) markers per cM, the correlation of true with estimated breeding value of selection candidates (accuracy) was greatest, 0.79 (0.85), when data from the same pure breed were used for training. When the training data set consisted of crossbreds, the accuracy ranged from 0.66 (0.79) to 0.74 (0.83) for the 2 marker densities, respectively. The admixed training data set resulted in nearly the same accuracies as when training was in the breed to which selection candidates belonged. However, accuracy was greatly reduced when genes from the target pure breed were not included in the admixed or crossbred population. This implies that, with high-density markers, admixed and crossbred populations can be used to develop GS prediction equations for all pure breeds that contributed to the population, without a substantial loss of accuracy compared with training on purebred data, even if breed origin has not been explicitly taken into account. In addition, using GS based on high-density marker data, purebreds can be accurately selected for crossbred performance without the need for pedigree or breed information. Results also showed that haplotype segments with strong linkage disequilibrium are shorter in crossbred and admixed populations than in purebreds, providing opportunities for QTL fine mapping.

Genomic selection using low-density marker panels.

Genomic selection (GS) using high-density single-nucleotide polymorphisms (SNPs) is promising to improve response to selection in populations that are under artificial selection. High-density SNP genotyping of all selection candidates each generation, however, may not be cost effective. Smaller panels with SNPs that show strong associations with phenotype can be used, but this may require separate SNPs for each trait and each population. As an alternative, we propose to use a panel of evenly spaced low-density SNPs across the genome to estimate genome-assisted breeding values of selection candidates in pedigreed populations. The principle of this approach is to utilize cosegregation information from low-density SNPs to track effects of high-density SNP alleles within families. Simulations were used to analyze the loss of accuracy of estimated breeding values from using evenly spaced and selected SNP panels compared to using all high-density SNPs in a Bayesian analysis. Forward stepwise selection and a Bayesian approach were used to select SNPs. Loss of accuracy was nearly independent of the number of simulated quantitative trait loci (QTL) with evenly spaced SNPs, but increased with number of QTL for the selected SNP panels. Loss of accuracy with evenly spaced SNPs increased steadily over generations but was constant when the smaller number individuals that are selected for breeding each generation were also genotyped using the high-density SNP panel. With equal numbers of low-density SNPs, panels with SNPs selected on the basis of the Bayesian approach had the smallest loss in accuracy for a single trait, but a panel with evenly spaced SNPs at 10 cM was only slightly worse, whereas a panel with SNPs selected by forward stepwise selection was inferior. Panels with evenly spaced SNPs can, however, be used across traits and populations and their performance is independent of the number of QTL affecting the trait and of the methods used to estimate effects in the training data and are, therefore, preferred for broad applications in pedigreed populations under artificial selection.

The effect of heritability estimates on high-density single nucleotide polymorphism analyses with related animals.

Analysis of high-density SNP data in outbred populations to identify SNP that are associated with a quantitative trait requires efficient ways to handle large volumes of data and analyses. When using mixed animal models to account for polygenic effects and relationships, genetic parameters are not known with certainty, but must be chosen to ensure proper evaluation of SNP across chromosomes and lines or breeds. The objectives of this study were to evaluate the influence of heritability on the estimates and significance of SNP effects, to develop efficient computational strategies for analysis of high-density SNP data with uncertain heritability estimates, and to develop strategies to combine SNP test results across lines or breeds. Data included sire SNP genotypes and mean progeny performance from 2 commercial broiler breeding lines. Association analyses were done by fitting each SNP separately as a fixed effect in an animal model, using a range of heritabilities. The heritability used had a limited impact on SNP effect estimates, but affected the SE of estimates and levels of significance. The shape of the frequency distribution of P-values for the test of SNP effects changed from a highly skewed L-shaped curve at low heritability to a right-skewed distribution at high heritability. The P-values for alternative heritabilities could, however, be derived without reanalysis based on a strong linear relationship (R(2) = 0.99) between differences in log-likelihood values of models with and without the SNP at different levels of heritabilities. With uncertain estimates of heritability, line-specific heritabilities that ensure proper evaluation of SNP effects across lines were determined by analysis of simulated sire genotypes and by permutation tests. Resulting heritability estimates were between those obtained from the entire breeding populations and those obtained from the data included in the sample data set. In conclusion, the uncertainty of heritability estimates has a limited impact on SNP effect estimates in association analyses, but a large impact on significance tests. The impact of heritability on tests can, however, be dealt with in a computationally efficient manner by using the strong linear relationship between model statistics under alternate levels of heritability. These approaches allow efficient analysis of large numbers of SNP for multiple traits and populations and pooling of results across populations.

Genetic associations of sow longevity with age at first farrowing, number of piglets weaned, and wean to insemination interval in the Finnish Landrace swine population.

The objective of the study was to estimate genetic parameters for length of productive life (LPL), and determine its genetic correlation with age at first farrowing (AFF), number of piglets weaned at first farrowing (NW), and first wean-to-insemination interval (W2I) in the Finnish Landrace swine population. Data from the Finnish national litter recording scheme were utilized to estimate the genetics of LPL, and genetic associations between LPL, AFF, NW, and W2I. Data from the Finnish Landrace sow records were utilized from farms that farrowed more than 20 gilts annually from 2000 through 2005. The data set included information from 11,222 sows, all of which had AFF and NW information available. The sows producing the records evaluated were daughters of 1,267 sires, and there were 3,684 animals in the pedigree when all of the sires were traced back to founder animals. All data were obtained from FABA Breeding (Vantaa, Finland). Multivariate Bayesian analysis of Gaussian, right censored Gaussian, and categorical traits was utilized to estimate (co)variance parameters of LPL, AFF, NW, and W2I of the sow. From these traits, AFF and NW were treated as Gaussian, LPL as right-censored Gaussian, and W2I as categorical traits. Estimated posterior means of heritabilities were 0.22, 0.16, 0.09, and 0.08 for LPL, AFF, NW, and W2I, respectively. A relatively large proportion of variance due to farm-year interaction was observed (posterior means of f(2) ranged between 0.03 and 0.26). The LPL was moderately genetically correlated with NW and AFF (posterior means were -0.20 and 0.36, respectively), whereas no clear association was found between W2I and LPL. Favorable genetic correlations between AFF and W2I and between NW and W2I were also observed. Additionally, an unfavorable genetic correlation between AFF and NW was observed in the present data set. Because LPL is genetically associated with other economically important prolificacy traits, it should be included in a multiple trait swine breeding value estimation system.

Introgressing multiple QTL in breeding programmes of limited size.

The ability to enrich a breed with favourable alleles from multiple unlinked quantitative trait loci (QTL) of a donor breed through marker-assisted introgression (MAI) in a population of limited size was evaluated by considering the effects of the proportion selected, the size of the marker intervals, the number of introgressed QTL and the uncertainty of QTL position. Informative flanking markers were used to select progeny with the largest expected number of donor QTL alleles over five generations of backcrossing and five generations of intercrossing. In the backcrossing phase, with 5% selected and 20 cM marker intervals for three QTL, there were sufficient backcross progeny that were heterozygous for all markers, and QTL frequencies dropped below 0.5 only because of double recombinants. For higher fractions selected, longer marker intervals, and more QTL, frequency reductions from 0.5 were greater and increased with additional generations of backcrossing. However, even with 20% selected, three QTL, and marker intervals of 5 or 20 cM, mean QTL frequencies in generation 5 were 0.35 and 0.30, sufficient to allow subsequent selection of QTL in the intercrossing phase. After five generations of intercrossing, over 90% of individuals were homozygous for all QTL, and 85% when five QTL were introgressed. The higher the proportions selected, the longer the marker intervals, and larger numbers of introgressed QTL increased the number of intercrossing generations required to achieve fixation of QTL. Location of the QTL in the marked intervals did not affect QTL frequencies or the proportion of QTL lost at the end of the introgression programme. In conclusion, introgressing multiple QTL can be accomplished in a MAI programme of limited size without requiring that all individuals selected during the backcrossing phase to be carriers of favourable alleles at all QTL.

The impact of genetic relationship information on genome-assisted breeding values.

The success of genomic selection depends on the potential to predict genome-assisted breeding values (GEBVs) with high accuracy over several generations without additional phenotyping after estimating marker effects. Results from both simulations and practical applications have to be evaluated for this potential, which requires linkage disequilibrium (LD) between markers and QTL. This study shows that markers can capture genetic relationships among genotyped animals, thereby affecting accuracies of GEBVs. Strategies to validate the accuracy of GEBVs due to LD are given. Simulations were used to show that accuracies of GEBVs obtained by fixed regression-least squares (FR-LS), random regression-best linear unbiased prediction (RR-BLUP), and Bayes-B are nonzero even without LD. When LD was present, accuracies decrease rapidly in generations after estimation due to the decay of genetic relationships. However, there is a persistent accuracy due to LD, which can be estimated by modeling the decay of genetic relationships and the decay of LD. The impact of genetic relationships was greatest for RR-BLUP. The accuracy of GEBVs can result entirely from genetic relationships captured by markers, and to validate the potential of genomic selection, several generations have to be analyzed to estimate the accuracy due to LD. The method of choice was Bayes-B; FR-LS should be investigated further, whereas RR-BLUP cannot be recommended.