A method for partitioning trends in genetic mean and variance to understand breeding practices.

BACKGROUND: In breeding programmes, the observed genetic change is a sum of the contributions of different selection paths represented by groups of individuals. Quantifying these sources of genetic change is essential for identifying the key breeding actions and optimizing breeding programmes. However, it is difficult to disentangle the contribution of individual paths due to the inherent complexity of breeding programmes. Here we extend the previously developed method for partitioning genetic mean by paths of selection to work both with the mean and variance of breeding values. METHODS: First, we extended the partitioning method to quantify the contribution of different paths to genetic variance assuming that the breeding values are known. Second, we combined the partitioning method with the Markov Chain Monte Carlo approach to draw samples from the posterior distribution of breeding values and use these samples for computing the point and interval estimates of partitions for the genetic mean and variance. We implemented the method in the R package AlphaPart. We demonstrated the method with a simulated cattle breeding programme. RESULTS: We show how to quantify the contribution of different groups of individuals to genetic mean and variance and that the contributions of different selection paths to genetic variance are not necessarily independent. Finally, we observed that the partitioning method under the pedigree-based model has some limitations, which suggests the need for a genomic extension. CONCLUSIONS: We presented a partitioning method to quantify sources of change in genetic mean and variance in breeding programmes. The method can help breeders and researchers understand the dynamics in genetic mean and variance in a breeding programme. The developed method for partitioning genetic mean and variance is a powerful method for understanding how different selection paths interact within a breeding programme and how they can be optimised.

Evaluation of low-density SNP panels and imputation for cost-effective genomic selection in four aquaculture species.

Genomic selection can accelerate genetic progress in aquaculture breeding programmes, particularly for traits measured on siblings of selection candidates. However, it is not widely implemented in most aquaculture species, and remains expensive due to high genotyping costs. Genotype imputation is a promising strategy that can reduce genotyping costs and facilitate the broader uptake of genomic selection in aquaculture breeding programmes. Genotype imputation can predict ungenotyped SNPs in populations genotyped at a low-density (LD), using a reference population genotyped at a high-density (HD). In this study, we used datasets of four aquaculture species (Atlantic salmon, turbot, common carp and Pacific oyster), phenotyped for different traits, to investigate the efficacy of genotype imputation for cost-effective genomic selection. The four datasets had been genotyped at HD, and eight LD panels (300-6,000 SNPs) were generated in silico. SNPs were selected to be: i) evenly distributed according to physical position ii) selected to minimise the linkage disequilibrium between adjacent SNPs or iii) randomly selected. Imputation was performed with three different software packages (AlphaImpute2, FImpute v.3 and findhap v.4). The results revealed that FImpute v.3 was faster and achieved higher imputation accuracies. Imputation accuracy increased with increasing panel density for both SNP selection methods, reaching correlations greater than 0.95 in the three fish species and 0.80 in Pacific oyster. In terms of genomic prediction accuracy, the LD and the imputed panels performed similarly, reaching values very close to the HD panels, except in the pacific oyster dataset, where the LD panel performed better than the imputed panel. In the fish species, when LD panels were used for genomic prediction without imputation, selection of markers based on either physical or genetic distance (instead of randomly) resulted in a high prediction accuracy, whereas imputation achieved near maximal prediction accuracy independently of the LD panel, showing higher reliability. Our results suggests that, in fish species, well-selected LD panels may achieve near maximal genomic selection prediction accuracy, and that the addition of imputation will result in maximal accuracy independently of the LD panel. These strategies represent effective and affordable methods to incorporate genomic selection into most aquaculture settings.

Assessment of long-term trends in genetic mean and variance after the introduction of genomic selection in layers: a simulation study.

Nucleus-based breeding programs are characterized by intense selection that results in high genetic gain, which inevitably means reduction of genetic variation in the breeding population. Therefore, genetic variation in such breeding systems is typically managed systematically, for example, by avoiding mating the closest relatives to limit progeny inbreeding. However, intense selection requires maximum effort to make such breeding programs sustainable in the long-term. The objective of this study was to use simulation to evaluate the long-term impact of genomic selection on genetic mean and variance in an intense layer chicken breeding program. We developed a large-scale stochastic simulation of an intense layer chicken breeding program to compare conventional truncation selection to genomic truncation selection optimized with either minimization of progeny inbreeding or full-scale optimal contribution selection. We compared the programs in terms of genetic mean, genic variance, conversion efficiency, rate of inbreeding, effective population size, and accuracy of selection. Our results confirmed that genomic truncation selection has immediate benefits compared to conventional truncation selection in all specified metrics. A simple minimization of progeny inbreeding after genomic truncation selection did not provide any significant improvements. Optimal contribution selection was successful in having better conversion efficiency and effective population size compared to genomic truncation selection, but it must be fine-tuned for balance between loss of genetic variance and genetic gain. In our simulation, we measured this balance using trigonometric penalty degrees between truncation selection and a balanced solution and concluded that the best results were between 45° and 65°. This balance is specific to the breeding program and depends on how much immediate genetic gain a breeding program may risk vs. save for the future. Furthermore, our results show that the persistence of accuracy is better with optimal contribution selection compared to truncation selection. In general, our results show that optimal contribution selection can ensure long-term success in intensive breeding programs using genomic selection.

Long-term comparison between index selection and optimal independent culling in plant breeding programs with genomic prediction.

In the context of genomic selection, we evaluated and compared breeding programs using either index selection or independent culling for recurrent selection of parents. We simulated a clonally propagated crop breeding program for 20 cycles using either independent culling or an economic index with two unfavourably correlated traits under selection. Cycle time from crossing to selection of parents was kept the same for both strategies. Both methods led to increasingly unfavourable genetic correlations between traits and, compared to independent culling, index selection led to larger changes in the genetic correlation between the two traits. When linkage disequilibrium was not considered, the two methods had similar losses of genetic diversity. Two independent culling approaches were evaluated, one using optimal culling levels and one using the same selection intensity for both traits. Optimal culling levels outperformed the same selection intensity even when traits had the same economic importance. Therefore, accurately estimating optimal culling levels is essential for maximizing gains when independent culling is performed. Once optimal culling levels are achieved, independent culling and index selection lead to comparable genetic gains.

Analysis of a large dataset reveals haplotypes carrying putatively recessive lethal and semi-lethal alleles with pleiotropic effects on economically important traits in beef cattle.

BACKGROUND: In livestock, deleterious recessive alleles can result in reduced economic performance of homozygous individuals in multiple ways, e.g. early embryonic death, death soon after birth, or semi-lethality with incomplete penetrance causing reduced viability. While death is an easy phenotype to score, reduced viability is not as easy to identify. However, it can sometimes be observed as reduced conception rates, longer calving intervals, or lower survival for live born animals. METHODS: In this paper, we searched for haplotypes that carry putatively recessive lethal or semi-lethal alleles in 132,725 genotyped Irish beef cattle from five breeds: Aberdeen Angus, Charolais, Hereford, Limousin, and Simmental. We phased the genotypes in sliding windows along the genome and used five tests to identify haplotypes with absence of or reduced homozygosity. Then, we associated the identified haplotypes with 44,351 insemination records that indicated early embryonic death, and postnatal survival records. Finally, we assessed haplotype pleiotropy by estimating substitution effects on estimates of breeding value for 15 economically important traits in beef production. RESULTS: We found support for one haplotype that carries a putatively recessive lethal (chromosome 16 in Simmental) and two haplotypes that carry semi-lethal alleles (chromosome 14 in Aberdeen Angus and chromosome 19 in Charolais), with population frequencies of 8.8, 15.2, and 14.4%, respectively. These three haplotypes showed pleiotropic effects on economically important traits for beef production. Their allele substitution effects are €2.30, €3.42, and €1.47 for the terminal index and €1.03, - €3.11, and - €0.88 for the replacement index, where the standard deviations for the terminal index are €22.52, €18.65, and €22.70 and for the replacement index they are €31.35, €29.82, and €35.79. We identified ZFAT as the candidate gene for semi-lethality in Aberdeen Angus, several candidate genes for the lethal Simmental haplotype, and no candidate genes for the semi-lethal Charolais haplotype. CONCLUSIONS: We analysed genotype, reproduction, survival, and production data to detect haplotypes that carry putatively recessive lethal or semi-lethal alleles in Irish beef cattle and identified one lethal and two semi-lethal haplotypes, which have pleiotropic effects on economically important traits in beef production.

Assessment of the performance of hidden Markov models for imputation in animal breeding.

BACKGROUND: In this paper, we review the performance of various hidden Markov model-based imputation methods in animal breeding populations. Traditionally, pedigree and heuristic-based imputation methods have been used for imputation in large animal populations due to their computational efficiency, scalability, and accuracy. Recent advances in the area of human genetics have increased the ability of probabilistic hidden Markov model methods to perform accurate phasing and imputation in large populations. These advances may enable these methods to be useful for routine use in large animal populations, particularly in populations where pedigree information is not readily available. METHODS: To test the performance of hidden Markov model-based imputation, we evaluated the accuracy and computational cost of several methods in a series of simulated populations and a real animal population without using a pedigree. First, we tested single-step (diploid) imputation, which performs both phasing and imputation. Second, we tested pre-phasing followed by haploid imputation. Overall, we used four available diploid imputation methods (fastPHASE, Beagle v4.0, IMPUTE2, and MaCH), three phasing methods, (SHAPEIT2, HAPI-UR, and Eagle2), and three haploid imputation methods (IMPUTE2, Beagle v4.1, and Minimac3). RESULTS: We found that performing pre-phasing and haploid imputation was faster and more accurate than diploid imputation. In particular, among all the methods tested, pre-phasing with Eagle2 or HAPI-UR and imputing with Minimac3 or IMPUTE2 gave the highest accuracies with both simulated and real data. CONCLUSIONS: The results of this study suggest that hidden Markov model-based imputation algorithms are an accurate and computationally feasible approach for performing imputation without a pedigree when pre-phasing and haploid imputation are used. Of the algorithms tested, the combination of Eagle2 and Minimac3 gave the highest accuracy across the simulated and real datasets.