329 research outputs found
International genomic evaluation methods for dairy cattle
<p>Abstract</p> <p>Background</p> <p>Genomic evaluations are rapidly replacing traditional evaluation systems used for dairy cattle selection. Higher reliabilities from larger genotype files promote cooperation across country borders. Genomic information can be exchanged across countries using simple conversion equations, by modifying multi-trait across-country evaluation (MACE) to account for correlated residuals originating from the use of foreign evaluations, or by multi-trait analysis of genotypes for countries that use the same reference animals.</p> <p>Methods</p> <p>Traditional MACE assumes independent residuals because each daughter is measured in only one country. Genomic MACE could account for residual correlations using daughter equivalents from genomic data as a fraction of the total in each country and proportions of bulls shared. MACE methods developed to combine separate within-country genomic evaluations were compared to direct, multi-country analysis of combined genotypes using simulated genomic and phenotypic data for 8,193 bulls in nine countries.</p> <p>Results</p> <p>Reliabilities for young bulls were much higher for across-country than within-country genomic evaluations as measured by squared correlations of estimated with true breeding values. Gains in reliability from genomic MACE were similar to those of multi-trait evaluation of genotypes but required less computation. Sharing of reference genotypes among countries created large residual correlations, especially for young bulls, that are accounted for in genomic MACE.</p> <p>Conclusions</p> <p>International genomic evaluations can be computed either by modifying MACE to account for residual correlations across countries or by multi-trait evaluation of combined genotype files. The gains in reliability justify the increased computation but require more cooperation than in previous breeding programs.</p
Identification of a nonsense mutation in APAF1 that is likely causal for a decrease in reproductive efficiency in Holstein dairy cattle
Genomic evaluations with many more genotypes
<p>Abstract</p> <p>Background</p> <p>Genomic evaluations in Holstein dairy cattle have quickly become more reliable over the last two years in many countries as more animals have been genotyped for 50,000 markers. Evaluations can also include animals genotyped with more or fewer markers using new tools such as the 777,000 or 2,900 marker chips recently introduced for cattle. Gains from more markers can be predicted using simulation, whereas strategies to use fewer markers have been compared using subsets of actual genotypes. The overall cost of selection is reduced by genotyping most animals at less than the highest density and imputing their missing genotypes using haplotypes. Algorithms to combine different densities need to be efficient because numbers of genotyped animals and markers may continue to grow quickly.</p> <p>Methods</p> <p>Genotypes for 500,000 markers were simulated for the 33,414 Holsteins that had 50,000 marker genotypes in the North American database. Another 86,465 non-genotyped ancestors were included in the pedigree file, and linkage disequilibrium was generated directly in the base population. Mixed density datasets were created by keeping 50,000 (every tenth) of the markers for most animals. Missing genotypes were imputed using a combination of population haplotyping and pedigree haplotyping. Reliabilities of genomic evaluations using linear and nonlinear methods were compared.</p> <p>Results</p> <p>Differing marker sets for a large population were combined with just a few hours of computation. About 95% of paternal alleles were determined correctly, and > 95% of missing genotypes were called correctly. Reliability of breeding values was already high (84.4%) with 50,000 simulated markers. The gain in reliability from increasing the number of markers to 500,000 was only 1.6%, but more than half of that gain resulted from genotyping just 1,406 young bulls at higher density. Linear genomic evaluations had reliabilities 1.5% lower than the nonlinear evaluations with 50,000 markers and 1.6% lower with 500,000 markers.</p> <p>Conclusions</p> <p>Methods to impute genotypes and compute genomic evaluations were affordable with many more markers. Reliabilities for individual animals can be modified to reflect success of imputation. Breeders can improve reliability at lower cost by combining marker densities to increase both the numbers of markers and animals included in genomic evaluation. Larger gains are expected from increasing the number of animals than the number of markers.</p
Inheritance of a mutation causing neuropathy with splayed forelimbs in Jersey cattle
A new undesirable genetic factor, neuropathy with splayed forelimbs (JNS), has been identified recently in the Jersey breed. Calves affected with JNS are unable to stand on splayed forelimbs that exhibit significant extensor rigidity and excessive lateral abduction at birth. Affected calves generally are alert at birth but exhibit neurologic symptoms, including spasticity of head and neck and convulsive behavior. Other symptoms reported include dislocated shoulders, congenital craniofacial anomalies, and degenerative myelopathy. Inheritance of an undesirable genetic factor was determined from a study of 16 affected calves reported by Jersey breeders across the United States. All of their pedigrees traced back on both paternal and maternal sides to a common ancestor born in 1995. Genotypes revealed that JNS is attributable to a specific haplotype on Bos taurus autosome 6. Currently 8.2% of the genotyped US Jersey population are carriers of the haplotype. Sequencing of the region of shared homozygosity revealed missense variant rs1116058914 at base 60,158,901 of the ARSUCD1.2 reference map as the most concordant with the genetic condition and the most likely cause. The single-base G to A substitution is in the coding region of the last exon of UCHL1, which is conserved across species. Mutations in humans and gene knockouts in mice cause similar recessive symptoms and muscular degeneration. Since December 2020, carrier status has been tracked using the identified haplotype and reported for all 459,784 genotyped Jersey animals. With random mating, about 2,200 affected calves per year with losses of about $250,000 would result from the 1.3 million US Jersey cows in the national population. Selection and mating programs can reduce numbers of JNS-affected births using either the haplotype status or a direct gene test in the future. Breeders should report calf abnormalities to their breed association to help discover new defects such as JNS
Accounting for genomic pre-selection in national BLUP evaluations in dairy cattle
<p>Abstract</p> <p>Background</p> <p>In future Best Linear Unbiased Prediction (BLUP) evaluations of dairy cattle, genomic selection of young sires will cause evaluation biases and loss of accuracy once the selected ones get progeny.</p> <p>Methods</p> <p>To avoid such bias in the estimation of breeding values, we propose to include information on all genotyped bulls, including the culled ones, in BLUP evaluations. Estimated breeding values based on genomic information were converted into genomic pseudo-performances and then analyzed simultaneously with actual performances. Using simulations based on actual data from the French Holstein population, bias and accuracy of BLUP evaluations were computed for young sires undergoing progeny testing or genomic pre-selection. For bulls pre-selected based on their genomic profile, three different types of information can be included in the BLUP evaluations: (1) data from pre-selected genotyped candidate bulls with actual performances on their daughters, (2) data from bulls with both actual and genomic pseudo-performances, or (3) data from all the genotyped candidates with genomic pseudo-performances. The effects of different levels of heritability, genomic pre-selection intensity and accuracy of genomic evaluation were considered.</p> <p>Results</p> <p>Including information from all the genotyped candidates, i.e. genomic pseudo-performances for both selected and culled candidates, removed bias from genetic evaluation and increased accuracy. This approach was effective regardless of the magnitude of the initial bias and as long as the accuracy of the genomic evaluations was sufficiently high.</p> <p>Conclusions</p> <p>The proposed method can be easily and quickly implemented in BLUP evaluations at the national level, although some improvement is necessary to more accurately propagate genomic information from genotyped to non-genotyped animals. In addition, it is a convenient method to combine direct genomic, phenotypic and pedigree-based information in a multiple-step procedure.</p
Large-scale genomic prediction using singular value decomposition of the genotype matrix
The impact of genetic relationship information on genomic breeding values in German Holstein cattle
<p>Abstract</p> <p>Background</p> <p>The impact of additive-genetic relationships captured by single nucleotide polymorphisms (SNPs) on the accuracy of genomic breeding values (GEBVs) has been demonstrated, but recent studies on data obtained from Holstein populations have ignored this fact. However, this impact and the accuracy of GEBVs due to linkage disequilibrium (LD), which is fairly persistent over generations, must be known to implement future breeding programs.</p> <p>Materials and methods</p> <p>The data set used to investigate these questions consisted of 3,863 German Holstein bulls genotyped for 54,001 SNPs, their pedigree and daughter yield deviations for milk yield, fat yield, protein yield and somatic cell score. A cross-validation methodology was applied, where the maximum additive-genetic relationship (<it>a</it><sub><it>max</it></sub>) between bulls in training and validation was controlled. GEBVs were estimated by a Bayesian model averaging approach (BayesB) and an animal model using the genomic relationship matrix (G-BLUP). The accuracy of GEBVs due to LD was estimated by a regression approach using accuracy of GEBVs and accuracy of pedigree-based BLUP-EBVs.</p> <p>Results</p> <p>Accuracy of GEBVs obtained by both BayesB and G-BLUP decreased with decreasing <it>a</it><sub><it>max </it></sub>for all traits analyzed. The decay of accuracy tended to be larger for G-BLUP and with smaller training size. Differences between BayesB and G-BLUP became evident for the accuracy due to LD, where BayesB clearly outperformed G-BLUP with increasing training size.</p> <p>Conclusions</p> <p>GEBV accuracy of current selection candidates varies due to different additive-genetic relationships relative to the training data. Accuracy of future candidates can be lower than reported in previous studies because information from close relatives will not be available when selection on GEBVs is applied. A Bayesian model averaging approach exploits LD information considerably better than G-BLUP and thus is the most promising method. Cross-validations should account for family structure in the data to allow for long-lasting genomic based breeding plans in animal and plant breeding.</p
Breeding value prediction for production traits in layer chickens using pedigree or genomic relationships in a reduced animal model
<p>Abstract</p> <p>Background</p> <p>Genomic selection involves breeding value estimation of selection candidates based on high-density SNP genotypes. To quantify the potential benefit of genomic selection, accuracies of estimated breeding values (EBV) obtained with different methods using pedigree or high-density SNP genotypes were evaluated and compared in a commercial layer chicken breeding line.</p> <p>Methods</p> <p>The following traits were analyzed: egg production, egg weight, egg color, shell strength, age at sexual maturity, body weight, albumen height, and yolk weight. Predictions appropriate for early or late selection were compared. A total of 2,708 birds were genotyped for 23,356 segregating SNP, including 1,563 females with records. Phenotypes on relatives without genotypes were incorporated in the analysis (in total 13,049 production records).</p> <p>The data were analyzed with a Reduced Animal Model using a relationship matrix based on pedigree data or on marker genotypes and with a Bayesian method using model averaging. Using a validation set that consisted of individuals from the generation following training, these methods were compared by correlating EBV with phenotypes corrected for fixed effects, selecting the top 30 individuals based on EBV and evaluating their mean phenotype, and by regressing phenotypes on EBV.</p> <p>Results</p> <p>Using high-density SNP genotypes increased accuracies of EBV up to two-fold for selection at an early age and by up to 88% for selection at a later age. Accuracy increases at an early age can be mostly attributed to improved estimates of parental EBV for shell quality and egg production, while for other egg quality traits it is mostly due to improved estimates of Mendelian sampling effects. A relatively small number of markers was sufficient to explain most of the genetic variation for egg weight and body weight.</p
Accuracy of genomic BLUP when considering a genomic relationship matrix based on the number of the largest eigenvalues: a simulation study.
International audienceAbstractBackgroundThe dimensionality of genomic information is limited by the number of independent chromosome segments (Me), which is a function of the effective population size. This dimensionality can be determined approximately by singular value decomposition of the gene content matrix, by eigenvalue decomposition of the genomic relationship matrix (GRM), or by the number of core animals in the algorithm for proven and young (APY) that maximizes the accuracy of genomic prediction. In the latter, core animals act as proxies to linear combinations of Me. Field studies indicate that a moderate accuracy of genomic selection is achieved with a small dataset, but that further improvement of the accuracy requires much more data. When only one quarter of the optimal number of core animals are used in the APY algorithm, the accuracy of genomic selection is only slightly below the optimal value. This suggests that genomic selection works on clusters of Me.ResultsThe simulation included datasets with different population sizes and amounts of phenotypic information. Computations were done by genomic best linear unbiased prediction (GBLUP) with selected eigenvalues and corresponding eigenvectors of the GRM set to zero. About four eigenvalues in the GRM explained 10% of the genomic variation, and less than 2% of the total eigenvalues explained 50% of the genomic variation. With limited phenotypic information, the accuracy of GBLUP was close to the peak where most of the smallest eigenvalues were set to zero. With a large amount of phenotypic information, accuracy increased as smaller eigenvalues were added.ConclusionsA small amount of phenotypic data is sufficient to estimate only the effects of the largest eigenvalues and the associated eigenvectors that contain a large fraction of the genomic information, and a very large amount of data is required to estimate the remaining eigenvalues that account for a limited amount of genomic information. Core animals in the APY algorithm act as proxies of almost the same number of eigenvalues. By using an eigenvalues-based approach, it was possible to explain why the moderate accuracy of genomic selection based on small datasets only increases slowly as more data are added
Accuracy of genomic breeding values in multi-breed dairy cattle populations
<p>Abstract</p> <p>Background</p> <p>Two key findings from genomic selection experiments are 1) the reference population used must be very large to subsequently predict accurate genomic estimated breeding values (GEBV), and 2) prediction equations derived in one breed do not predict accurate GEBV when applied to other breeds. Both findings are a problem for breeds where the number of individuals in the reference population is limited. A multi-breed reference population is a potential solution, and here we investigate the accuracies of GEBV in Holstein dairy cattle and Jersey dairy cattle when the reference population is single breed or multi-breed. The accuracies were obtained both as a function of elements of the inverse coefficient matrix and from the realised accuracies of GEBV.</p> <p>Methods</p> <p>Best linear unbiased prediction with a multi-breed genomic relationship matrix (GBLUP) and two Bayesian methods (BAYESA and BAYES_SSVS) which estimate individual SNP effects were used to predict GEBV for 400 and 77 young Holstein and Jersey bulls respectively, from a reference population of 781 and 287 Holstein and Jersey bulls, respectively. Genotypes of 39,048 SNP markers were used. Phenotypes in the reference population were de-regressed breeding values for production traits. For the GBLUP method, expected accuracies calculated from the diagonal of the inverse of coefficient matrix were compared to realised accuracies.</p> <p>Results</p> <p>When GBLUP was used, expected accuracies from a function of elements of the inverse coefficient matrix agreed reasonably well with realised accuracies calculated from the correlation between GEBV and EBV in single breed populations, but not in multi-breed populations. When the Bayesian methods were used, realised accuracies of GEBV were up to 13% higher when the multi-breed reference population was used than when a pure breed reference was used. However no consistent increase in accuracy across traits was obtained.</p> <p>Conclusion</p> <p>Predicting genomic breeding values using a genomic relationship matrix is an attractive approach to implement genomic selection as expected accuracies of GEBV can be readily derived. However in multi-breed populations, Bayesian approaches give higher accuracies for some traits. Finally, multi-breed reference populations will be a valuable resource to fine map QTL.</p
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