Opportunities and computational challenges in large-scale whole genome sequencing data analysis.

Genomic selection has been used in animal breeding for c. 15 years and continues to be an important tool in predicting genetic merit in livestock populations. The dairy cattle industry was the first to adopt genomic selection, initially based on some 50K SNP arrays for thousands of animals.

A major QTL region associated with powdery mildew resistance in leaves and fruits of the reconstructed garden strawberry.

Multiple QTLs for powdery mildew resistance were identified in a pre-breeding population derived from the octoploid progenitor species of garden strawberry, including a stable major novel factor on chromosome 3B. Powdery mildew (PM), caused by the biotrophic fungal pathogen Podosphaera aphanis, poses an increasing threat to garden strawberry (Fragaria × ananassa) production worldwide. While a few commercial cultivars exhibit partial resistance, fungicide application remains essential for managing PM outbreaks.

A computationally efficient algorithm to leverage average information REML for (co)variance component estimation in the genomic era.

Background: Methods for estimating variance components (VC) using restricted maximum likelihood (REML) typically require elements from the inverse of the coefficient matrix of the mixed model equations (MME). As genomic information becomes more prevalent, the coefficient matrix of the MME becomes denser, presenting a challenge for analyzing large datasets. Thus, computational algorithms based on iterative solving and Monte Carlo approximation of the inverse of the coefficient matrix become appealing.

Marker weighting improves single-step genomic prediction reliabilities of udder health traits in Nordic Red and Jersey dairy cattle populations.

The standard single-step genomic prediction model assumes that all SNP markers explain an equal amount of genetic variance, which, however, may not be true. This is because SNPs are located in or near different genes with different functions. Therefore, it seems logical to consider SNP marker-specific weights when predicting genomic breeding values.

A computationally feasible multi-trait single-step genomic prediction model with trait-specific marker weights.

Background: Regions of genome-wide marker data may have differing influences on the evaluated traits. This can be reflected in the genomic models by assigning different weights to the markers, which can enhance the accuracy of genomic prediction. However, the standard multi-trait single-step genomic evaluation model can be computationally infeasible when the traits are allowed to have different marker weights.

Segregation between breeds and local breed proportions in genetic and genomic models for crossbreds.

Background: The breeding value of a crossbred individual can be expressed as the sum of the contributions from each of the contributing pure breeds. In theory, the breeding value should account for segregation between breeds, which results from the difference in the mean contribution of loci between breeds, which in turn is caused by differences in allele frequencies between breeds. However, with multiple generations of crossbreeding, how to account for breed segregation in genomic models that split the breeding value of crossbreds based on breed origin of alleles (BOA) is not known.

Efficient large-scale single-step evaluations and indirect genomic prediction of genotyped selection candidates.

Background: Single-step genomic best linear unbiased prediction (ssGBLUP) models allow the combination of genomic, pedigree, and phenotypic data into a single model, which is computationally challenging for large genotyped populations. In practice, genotypes of animals without their own phenotype and progeny, so-called genotyped selection candidates, can become available after genomic breeding values have been estimated by ssGBLUP. In some breeding programmes, genomic estimated breeding values (GEBV) for these animals should be known shortly after obtaining genotype information but recomputing GEBV using the full ssGBLUP takes too much time.

A computationally efficient method for approximating reliabilities in large-scale single-step genomic prediction.

Background: In this study, computationally efficient methods to approximate the reliabilities of genomic estimated breeding values (GEBV) in a single-step genomic prediction model including a residual polygenic (RPG) effect are described. In order to calculate the reliabilities of the genotyped animals, a single nucleotide polymorphism best linear unbiased prediction (SNPBLUP) or a genomic BLUP (GBLUP), was used, where two alternatives to account for the RPG effect were tested. In the direct approach, the genomic model included the RPG effect, while in the blended method, it did not but an index was used to weight the genomic and pedigree-based BLUP (PBLUP) reliabilities.

Invited review: Reliability computation from the animal model era to the single-step genomic model era.

The calculation of exact reliabilities involving the inversion of mixed model equations poses a heavy computational challenge when the system of equations is large. This has prompted the development of different approximation methods. We give an overview of the various methods and computational approaches in calculating reliability from the era before the animal model to the era of single-step genomic models.

Single-step genomic BLUP with many metafounders.

Single-step genomic BLUP (ssGBLUP) model for routine genomic prediction of breeding values is developed intensively for many dairy cattle populations. Compatibility between the genomic () and the pedigree () relationship matrices remains an important challenge required in ssGBLUP. The compatibility relates to the amount of missing pedigree information.

Local breed proportions and local breed heterozygosity in genomic predictions for crossbred dairy cows.

For genomic prediction of crossbred animals, models that account for the breed origin of alleles (BOA) in marker genotypes can allow the effects of marker alleles to differ depending on their ancestral breed. Previous studies have shown that genomic estimated breeding values for crossbred cows can be calculated using the marker effects that are estimated in the contributing pure breeds and combined based on estimated BOA in the genotypes of the crossbred cows. In the presented study, we further exploit the BOA information for improving the prediction of genomic breeding values of crossbred dairy cows.

Single-step genomic BLUP with genetic groups and automatic adjustment for allele coding.

Background: Genomic estimated breeding values (GEBV) by single-step genomic BLUP (ssGBLUP) are affected by the centering of marker information used. The use of a fixed effect called J factor will lead to GEBV that are unaffected by the centering used. We extended the use of a single J factor to a group of J factors.

Breeding value reliabilities for multiple-trait single-step genomic best linear unbiased predictor.

Approximate multistep methods to calculate reliabilities for estimated breeding values in large genetic evaluations were developed for single-trait (ST-RA) and multitrait (MT-RA) single-step genomic BLUP (ssGBLUP) models. First, a traditional animal model was used to estimate the amount of nongenomic information for the genotyped animals. Second, this information was used with genomic data in a genomic BLUP model (genomic BLUP/SNP-BLUP) to approximate the total amount of information and ssGBLUP reliabilities for the genotyped animals.

Single-step genomic evaluation of Russian dairy cattle using internal and external information.

Genomic data are widely used in predicting the breeding values of dairy cattle. The accuracy of genomic prediction depends on the size of the reference population and how related the candidate animals are to it. For populations with limited numbers of progeny-tested bulls, the reference populations must include cows and data from external populations.

Efficient Monte Carlo algorithm for restricted maximum likelihood estimation of genetic parameters.

Monte Carlo (MC) methods have been found useful in estimation of variance parameters for large data and complex models with many variance components (VC), with respect to both computer memory and computing time. A disadvantage has been a fluctuation in round-to-round values of estimates that makes the estimation of convergence challenging. Furthermore, with Newton-type algorithms, the approximate Hessian matrix might have sufficient accuracy, but the inaccuracy in the gradient vector exaggerates the round-to-round fluctuation to intolerable.

Genomic selection strategies for breeding adaptation and production in dairy cattle under climate change.

Livestock production both contributes to and is affected by global climate change, and substantial modifications will be required to increase its climate resilience. In this context, reliance on dominant commercial livestock breeds, featuring small effective population sizes, makes current production strategies vulnerable if their production is restricted to environments, which may be too costly to support under future climate scenarios. The adaptability of animal populations to future environments will therefore become important.

Joint breeding value evaluation for fertility in Finnish and Norwegian blue foxes.

We developed a multiple-trait animal model for blue fox fertility evaluation and estimated genetic parameters simultaneously for seven traits: first three litter sizes (LS), pregnancy rate (PREG), whelping success (WHELP), grading size (gSI) and fur quality (gQU). Grading size and quality were included into the new multiple-trait model as correlated traits. Litter size of the first parity had the highest unfavourable genetic correlations with gSI (-0.

Single step genomic evaluation for female fertility in Nordic Red dairy cattle.

Joint Nordic (Denmark, Finland, Sweden) genetic evaluation of female fertility is currently based on the multiple trait multilactation animal model (BLUP). Here, single step genomic model (ssGBLUP) was applied for the Nordic Red dairy cattle fertility evaluation. The 11 traits comprised of nonreturn rate and days from first to last insemination in heifers and first three parities, and days from calving to first insemination in the first three parities.

Large-scale genomic prediction using singular value decomposition of the genotype matrix.

Background: For marker effect models and genomic animal models, computational requirements increase with the number of loci and the number of genotyped individuals, respectively. In the latter case, the inverse genomic relationship matrix (GRM) is typically needed, which is computationally demanding to compute for large datasets. Thus, there is a great need for dimensionality-reduction methods that can analyze massive genomic data.

Single-step SNP-BLUP with on-the-fly imputed genotypes and residual polygenic effects.

Background: Single-step genomic best linear unbiased prediction (BLUP) evaluation combines relationship information from pedigree and genomic marker data. The inclusion of the genomic information into mixed model equations requires the inverse of the combined relationship matrix [Formula: see text], which has a dense matrix block for genotyped animals.

Methods: To avoid inversion of dense matrices, single-step genomic BLUP can be transformed to single-step single nucleotide polymorphism BLUP (SNP-BLUP) which have observed and imputed marker coefficients.

Across-country test-day model evaluations for Holstein, Nordic Red Cattle, and Jersey.

Three random regression models were developed for routine genetic evaluation of Danish, Finnish, and Swedish dairy cattle. Data included over 169 million test-day records with milk, protein, and fat yield observations from over 8.7 million dairy cows of all breeds.

Genomic relationships based on X chromosome markers and accuracy of genomic predictions with and without X chromosome markers.

Background: Although the X chromosome is the second largest bovine chromosome, markers on the X chromosome are not used for genomic prediction in some countries and populations. In this study, we presented a method for computing genomic relationships using X chromosome markers, investigated the accuracy of imputation from a low density (7K) to the 54K SNP (single nucleotide polymorphism) panel, and compared the accuracy of genomic prediction with and without using X chromosome markers.

Methods: The impact of considering X chromosome markers on prediction accuracy was assessed using data from Nordic Holstein bulls and different sets of SNPs: (a) the 54K SNPs for reference and test animals, (b) SNPs imputed from the 7K to the 54K SNP panel for test animals, (c) SNPs imputed from the 7K to the 54K panel for half of the reference animals, and (d) the 7K SNP panel for all animals.

Employing a Monte Carlo algorithm in Newton-type methods for restricted maximum likelihood estimation of genetic parameters.

Estimation of variance components by Monte Carlo (MC) expectation maximization (EM) restricted maximum likelihood (REML) is computationally efficient for large data sets and complex linear mixed effects models. However, efficiency may be lost due to the need for a large number of iterations of the EM algorithm. To decrease the computing time we explored the use of faster converging Newton-type algorithms within MC REML implementations.

A comparison of approaches to estimate the inbreeding coefficient and pairwise relatedness using genomic and pedigree data in a sheep population.

Genome-wide SNP data provide a powerful tool to estimate pairwise relatedness among individuals and individual inbreeding coefficient. The aim of this study was to compare methods for estimating the two parameters in a Finnsheep population based on genome-wide SNPs and genealogies, separately. This study included ninety-nine Finnsheep in Finland that differed in coat colours (white, black, brown, grey, and black/white spotted) and were from a large pedigree comprising 319 119 animals.

Allele coding in genomic evaluation.

Background: Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used.