Pedigree-based Relationship Research Articles

Exploring unknown parent groups and metafounders in single-step genomic best linear unbiased prediction: Insights from a simulated cattle population

This study explores how the metafounder (MF) concept enhances genetic evaluations in dairy cattle populations using single-step genomic best linear unbiased prediction (ssGBLUP). By improving the consideration of relationships among founder populations, MF ensures accurate alignment of pedigree and genomic relationships. The research aims to propose a method for grouping MF based on genotypic information, assess different approaches for estimating the gamma matrix, and compare unknown parent groups (UPG) and MF methodologies across various scenarios, including those with low and high pedigree completeness based on a simulated dairy cattle population. In the scenario where unknown ancestors are rare, the impact of UPG or MF on breeding values is minimal but MF still performs slightly better compared with UPG. The scenario with lower genotyping rates and more unknown parents shows significant differences in evaluations with and without UPG and also compared with MF. The study shows that ssGBLUP evaluations where UPG are considered via Quaas-Pollak-transformation in the pedigree-based and genomic relationship matrix (UPG_fullQP) results in double counting and subsequently in a pronounced bias and overdispersion. Another focus is on the estimation of the gamma matrix, emphasizing the importance of crossbred genotypes for accuracy. Challenges emerge in classifying animals into subpopulations and further into MF or UPG, but the method used in this study, which is based on genotypes, results in predictions which are comparable to those obtained using the true subpopulations for the assignment. Estimated validation results using the linear regression method confirm the superior performance of MF evaluations, although differences compared with true validations are smaller. Notably, UPG_fullQP's extreme bias is less evident in routine validation statistics.

Genetic and genomic evaluation of age at first calving in Italian Holsteins

Age at first calving (AFC) represents the non-productive period of around 2 yr in Holstein cows and thus it has a relevant impact on the cost of rearing replacements in the dairy herd. In the present study we aimed at evaluating genetic and genomic aspects of AFC in the Italian Holstein population. Data of 4,206,218 heifers with first calving between 1996 and 2020 were used. Age at first calving averaged 26.09 ± 3.07 mo and decreased across years. Heritability was estimated using a linear animal model which included the fixed effects of herd-year-season of birth and classes of gestation length, and the random animal additive genetic effect fitted to a pedigree-based relationship matrix. Estimated breeding values (EBV) and genomically enhanced breeding values (GEBV) were obtained, and they were standardized to mean 100 and standard deviation 5, where animals above the mean are those contributing to reduce AFC. Heritability estimates of AFC ranged from 0.031 to 0.045. The trend of sires' GEBV was favorable and indicated a reduced AFC across years. Approximate genetic correlations between GEBV of AFC and GEBV of other economically important traits were calculated on a subset of genotyped females born after 2015. Moderate favorable associations of AFC with production traits (0.39 to 0.51), udder depth (0.40), interval from first to last insemination in heifer (-0.43), and longevity (0.34) were assessed. Overall, the greatest lifetime productive performances and most favorable days open in first lactation were observed when heifers calved at 22-23 mo. On the other hand, progeny of sires with GEBV of AFC above the mean yielded more milk, fat, and protein in first lactation, and had shorter days open than progeny of sires with GEBV of AFC below the mean. Results suggested that breeding strategies to improve AFC should be pursued, also considering genetic correlations between AFC and traits which are already part of the Italian Holstein breeding objective. The inclusion of AFC in an aggregate index is expected to contribute to enhance farm income.

The Estimation of Genetic Parameters for Chronic Progressive Lymphedema and Body Traits in the Rhenish German Draught Horse.

Chronic progressive lymphedema (CPL) is a prevalent and progressive disease in Rhenish German draught horses. The objective of our follow-up study was to evaluate the heritability of this disease in Rhenish German draught horses using pedigree-based and genomic relationship matrices. We employed linear and threshold animal models. Models included the random animal effect and effects of breeding association, coat colour, sex, and age within sex, and farm-related factors, on CPL scores. In addition, we estimated heritabilities in models assuming censoring for data when horses were below an age of 1-15 years. The heritabilities of CPL scores across all ages were 0.595 ± 0.131 and 0.482 ± 0.105 in the threshold and linear animal model with pedigree-based relationship matrices, respectively. The restriction of data to horses with a minimum age at examination or accounting for censored data in younger animals showed an increase in heritabilities of CPL scores up to 0.788 ± 0.168 (threshold model) and 0.752 ± 0.153 (linear model) at an age of 7-8 years. Analyses including genomic relationship matrices yielded very similar estimates, but with smaller standard errors than pedigree-based analyses. Heritabilities in threshold models for CPL prevalence (CPL-bin-score) and the number of affected limbs (CPL-bin-sum) were 0.176-0.189 ± 0.061-0.064 and 0.375-0.433 ± 0.164-0.170, respectively. We were able to show moderately to highly positive genetic correlations between the CPL score and cannon bone circumference (0.529-0.825), height at withers (0.338-0.555), and skinfold thickness (0.241-0.517). Using the dichotomous trait for the CPL score and the genomic relationship matrix resulted in corresponding estimates of 0.868, 0.793, and 0.784, respectively. This study showed the great importance of additive genetic variation influencing the expression of chronic progressive lymphedema in Rhenish German draught horses. Therefore, further research is warranted to implement breeding programmes in a small breeding population that exploit the potential of additive genetic differences among animals for reducing the prevalence and severity of lesions of this incurable disease.

Genomic evaluation for breeding and genetic management in Cordia africana, a multipurpose tropical tree species

BackgroundPlanting tested forest reproductive material is crucial to ensure the increased resilience of intensively managed productive stands for timber and wood product markets under climate change scenarios. Single-step Genomic Best Linear Unbiased Prediction (ssGBLUP) analysis is a cost-effective option for using genomic tools to enhance the accuracy of predicted breeding values and genetic parameter estimation in forest tree species. Here, we tested the efficiency of ssGBLUP in a tropical multipurpose tree species, Cordia africana, by partial population genotyping. A total of 8070 trees from three breeding seedling orchards (BSOs) were phenotyped for height. We genotyped 6.1% of the phenotyped individuals with 4373 single nucleotide polymorphisms. The results of ssGBLUP were compared with pedigree-based best linear unbiased prediction (ABLUP) and genomic best linear unbiased prediction (GBLUP), based on genetic parameters, theoretical accuracy of breeding values, selection candidate ranking, genetic gain, and predictive accuracy and prediction bias.ResultsGenotyping a subset of the study population provided insights into the level of relatedness in BSOs, allowing better genetic management. Due to the inbreeding detected within the genotyped provenances, we estimated genetic parameters both with and without accounting for inbreeding. The ssGBLUP model showed improved performance in terms of additive genetic variance and theoretical breeding value accuracy. Similarly, ssGBLUP showed improved predictive accuracy and lower bias than the pedigree-based relationship matrix (ABLUP).ConclusionsThis study of C. africana, a species in decline due to deforestation and selective logging, revealed inbreeding depression. The provenance exhibiting the highest level of inbreeding had the poorest overall performance. The use of different relationship matrices and accounting for inbreeding did not substantially affect the ranking of candidate individuals. This is the first study of this approach in a tropical multipurpose tree species, and the analysed BSOs represent the primary effort to breed C. africana.

Estimation of the genetic parameters for temperament in Haflinger horses based on the results of a character test using a pedigree-based relationship matrix

Literature provides indications that the personality and temperament of a horse are sufficiently genetically determined. This background was the impetus to continue collecting phenotypic information on the temperament in the South Tyrolean Haflinger horses, not only to have marketing tools but also to be able to estimate genetic parameters for a future genetic evaluation. The latter should open the possibility to include temperament traits in the breeding goal. Therefore, the aim of the present study was to consider for the very first-time phenotypic information from character testing for estimating genetic parameters for temperament in Haflinger horses. For the present study, data from routine character testing of 210 South Tyrolean Haflinger mares between 2019 and 2021 were considered. A multivariate estimation of heritability (h2) and genetic correlations (r) was carried out for the criteria ‘Interest’, ‘Activity’ and ‘Excitement’. In addition, univariate and bivariate estimation runs were also carried out. The pedigree-based heritability for the behavioural trait Interest was lowest with 0.07 and a standard error of ±0.04. For the other two criteria, Activity and Excitement, h2 was 0.19 ± 0.05 and 0.21 ± 0.04, respectively. The genetic correlation between Interest and Activity and between Interest and Excitement was in both cases negative with −0.52 and −0.61, respectively while the genetic correlation between Excitement and Activity was positive (0.99). Results of the present study highlight the potential of considering temperament traits in breeding of Haflinger horses.

Impact of kinship matrices on genetic gain and inbreeding with optimum contribution selection in a genomic dairy cattle breeding program

BackgroundGenomic selection has increased genetic gain in dairy cattle, but in some cases it has resulted in higher inbreeding rates. Therefore, there is need for research on efficient management of inbreeding in genomically-selected dairy cattle populations, especially for local breeds with a small population size. Optimum contribution selection (OCS) minimizes the increase in average kinship while it maximizes genetic gain. However, there is no consensus on how to construct the kinship matrix used for OCS and whether it should be based on pedigree or genomic information. VanRaden’s method 1 (VR1) is a genomic relationship matrix in which centered genotype scores are scaled with the sum of 2p(1-p) where p is the reference allele frequency at each locus, and VanRaden’s method 2 (VR2) scales each locus with 2p(1-p), thereby giving greater weight to loci with a low minor allele frequency. We compared the effects of nine kinship matrices on genetic gain, kinship, inbreeding, genetic diversity, and minor allele frequency when applying OCS in a simulated small dairy cattle population. We used VR1 and VR2, each using base animals, all genotyped animals, and the current generation of animals to compute reference allele frequencies. We also set the reference allele frequencies to 0.5 for VR1 and the pedigree-based relationship matrix. We constrained OCS to select a fixed number of sires per generation for all scenarios. Efficiency of the different matrices were compared by calculating the rate of genetic gain for a given rate of increase in average kinship.ResultsWe found that: (i) genomic relationships were more efficient than pedigree-based relationships at managing inbreeding, (ii) reference allele frequencies computed from base animals were more efficient compared to reference allele frequencies computed from recent animals, and (iii) VR1 was slightly more efficient than VR2, but the difference was not statistically significant.ConclusionsUsing genomic relationships for OCS realizes more genetic gain for a given amount of kinship and inbreeding than using pedigree relationships when the number of sires is fixed. For a small genomic dairy cattle breeding program, we recommend that the implementation of OCS uses VR1 with reference allele frequencies estimated either from base animals or old genotyped animals.

Genetic and genomic evaluation for resistance to white spot syndrome virus in post-larvae of Pacific white shrimp (Litopenaeus vannamei)

The objective of the present study was to compare genetic evaluations with pedigree- and genomic-based for the time of death of post-inoculation (TD) and survival considered as a binary variable (1 = survivor, 0 = dead) (BS) to white spot syndrome obtained in a controlled experimental challenge. In seven tanks were seed a total 6132 shrimps, of which the genotypes of 1685 were obtained using a commercial 50 K SNP panel. A total of 176 families were formed from a Sire: Dam ratio of 1:2. In the challenge test, the organisms were inoculated per os with macerated shrimp tissue with a viral load of 1 × 106 copies/g of tissue. The inoculum was supplied in two doses (first of 6% and second of 4% of the biomass in each tank) whit 12 h of difference. Four approaches were used for estimating variance components and calculating genetic or genomic estimated breeding values: 1) PBLUP-1 is an animal model fitted using a pedigree-based kinship matrix using only parent-progeny relationships from individuals from the latest generation; 2) PBLUP-All is the same as above but using the genealogy from 19 generations; 3) GBLUP is an animal model fitted using a genomic-based relationship matrix including genotyped animals only, and 4) ssGBLUP is an animal model fitted using a blend between the pedigree and genomic relationship matrix. The heritability values obtained for TD and BS with the four approaches ranged from 0.072 to 0.105 and 0.069 to 0.095, respectively. The heritability estimators obtained with genomic information were slightly higher than those obtained with only pedigree information. PBLUP-All and ssGBLUP present proportionally lower standard errors than PBLUP-1 and GBLUP. The use of genomic information (GBLUP and ssGBLUP) increased the mean accuracy of estimated breeding values by an average of 38% and 54% concerning methods that only used phenotypic information (PBLUP-1 and PBLUP-ALL). Using a 50 K SNP genotyping panel and deep pedigree information increased heritability estimation of traits associated with resistance to white spot syndrome virus in Pacific white shrimp. Using genomic information substantially improves the accuracy of estimated breeding values when using ssGBLUP compared to pedigree-based methods. Genomic selection will allow individual selection within-family by predicting the genetic values of animals not exposed to the white spot syndrome virus.

Genomic selection in algae with biphasic lifecycles: A Saccharina latissima (sugar kelp) case study

IntroductionSugar kelp (Saccharina latissima) has a biphasic life cycle, allowing selection on both thediploid sporophytes (SPs) and haploid gametophytes (GPs).MethodsWe trained a genomic selection (GS) model from farm-tested SP phenotypic data and used a mixed-ploidy additive relationship matrix to predict GP breeding values. Topranked GPs were used to make crosses for further farm evaluation. The relationship matrix included 866 individuals: a) founder SPs sampled from the wild; b) progeny GPs from founders; c) Farm-tested SPs crossed from b); and d) progeny GPs from farm-tested SPs. The complete pedigree-based relationship matrix was estimated for all individuals. A subset of founder SPs (n = 58) and GPs (n = 276) were genotyped with Diversity Array Technology and whole genome sequencing, respectively. We evaluated GS prediction accuracy via cross validation for SPs tested on farm in 2019 and 2020 using a basic GBLUP model. We also estimated the general combining ability (GCA) and specific combining ability (SCA) variances of parental GPs. A total of 11 yield-related and morphology traits were evaluated.ResultsThe cross validation accuracies for dry weight per meter (r ranged from 0.16 to 0.35) and wet weight per meter (r ranged 0.19 to 0.35) were comparable to GS accuracy for yield traits in terrestrial crops. For morphology traits, cross validation accuracy exceeded 0.18 in all scenarios except for blade thickness in the second year. Accuracy in a third validation year (2021) was 0.31 for dry weight per meter over a confirmation set of 87 individuals.DiscussionOur findings indicate that progress can be made in sugar kelp breeding by using genomic selection.

Comparing Methods to Select Candidates for Re-Genotyping to Impute Higher-Density Genotype Data in a Japanese Black Cattle Population: A Case Study

As optimization methods to identify the best animals for dense genotyping to construct a reference population for genotype imputation, the MCA and MCG methods, which use the pedigree-based additive genetic relationship matrix (A matrix) and the genomic relationship matrix (G matrix), respectively, have been proposed. We assessed the performance of MCA and MCG methods using 575 Japanese Black cows. Pedigree data were provided to trace back up to five generations to construct the A matrix with changing the pedigree depth from 1 to 5 (five MCA methods). Genotype information on 36,426 single-nucleotide polymorphisms was used to calculate the G matrix based on VanRaden's methods 1 and 2 (two MCG methods). The MCG always selected one cow per iteration, while MCA sometimes selected multiple cows. The number of commonly selected cows between the MCA and MCG methods was generally lower than that between different MCA methods or between different MCG methods. For the studied population, MCG appeared to be more reasonable than MCA in selecting cows as a reference population for higher-density genotype imputation to perform genomic prediction and a genome-wide association study.

A Note on the Conditioning of the H-1 Matrix Used in Single-Step GBLUP.

The single-step genomic BLUP (ssGBLUP) is used worldwide for the simultaneous genetic evaluation of genotyped and non-genotyped animals. It is easily extendible to all BLUP models by replacing the pedigree-based additive genetic relationship matrix (A) with an augmented pedigree-genomic relationship matrix (H). Theoretically, H does not introduce any artificially inflated variance. However, inflated genetic variances have been observed due to the incomparability between the genomic relationship matrix (G) and A used in H. Usually, G is blended and tuned with A22 (the block of A for genotyped animals) to improve its numerical condition and compatibility. If deflation/inflation is still needed, a common approach is weighting G-1-A22-1 in the form of τG-1-ωA22-1, added to A-1 to form H-1. In some situations, this can violate the conditional properties upon which H is built. Different ways of weighting the H-1 components (A-1, G-1, A22-1, and H-1 itself) were studied to avoid/minimise the violations of the conditional properties of H. Data were simulated on ten populations and twenty generations. Responses to weighting different components of H-1 were measured in terms of the regression of phenotypes on the estimated breeding values (the lower the slope, the higher the inflation) and the correlation between phenotypes and the estimated breeding values (predictive ability). Increasing the weight on H-1 increased the inflation. The responses to weighting G-1 were similar to those for H-1. Increasing the weight on A-1 (together with A22-1) was not influential and slightly increased the inflation. Predictive ability is a direct function of the slope of the regression line and followed similar trends. Responses to weighting G-1-A22-1 depend on the inflation/deflation of evaluations from A-1 to H-1 and the compatibility of the two matrices with the heritability used in the model. One possibility is a combination of weighting G-1-A22-1 and weighting H-1. Given recent advances in ssGBLUP, conditioning H-1 might become an interim solution from the past and then not be needed in the future.

Genetic and nongenetic variation of heifer fertility in Italian Holstein cattle

Excellent fertility performance is important to maximize farmers' profit and to reduce the number of culled animals. Although female fertility of adult cows has been included in Italian Holstein breeding objectives since 2009, little has been done to quantify genetic variation of heifer fertility characteristics so far. The aim of the present study was to estimate genetic parameters of 4 fertility traits in nulliparous Italian Holstein heifers and to develop an aggregate selection index to improve heifer fertility. Data were retrieved from the national fertility database and included information on insemination, calving, and pregnancy diagnosis dates. The investigated phenotypes (mean ± standard deviation) were age at first insemination (AFI, mo; 17.25 ± 2.89), nonreturn rate at 56 d from the first insemination (NRR56, binary; 0.78 ± 0.41), conception rate at first insemination (CR, binary; 0.61 ± 0.49), and interval from first to last insemination (IFL, d; 26.09 ± 51.85). Genetic parameters were estimated using a 4-trait animal model that included the following fixed effects: herd-year of birth and month of birth for AFI, and herd-year-season of birth and month-year of insemination for IFL, NRR56, and CR; the animal additive genetic effect (fitted to the pedigree-based relationship matrix) was considered as a random term. An aggregate index was developed from the estimated additive genetic (co)variance matrix by considering CR as the breeding goal and AFI, NRR56, and IFL as selection criteria. Heritability estimates from average covariance matrices ranged from 0.012 (CR) to 0.015 (IFL), with the exception of AFI (0.071). Conception rate at first insemination was strongly correlated with both IFL (−0.730) and NRR56 (0.668), and weakly to AFI (−0.065), and the relative emphasis placed on each selection criteria in the aggregate index was 10%, 47%, and 43% for AFI, IFL, and NRR56, respectively. The results of the present study suggest that heifer fertility should be considered as an additional trait in the breeding objectives of Italian Holstein.

Genomic selection for resistance to mammalian bark stripping and associated chemical compounds in radiata pine.

The integration of genomic data into genetic evaluations can facilitate the rapid selection of superior genotypes and accelerate the breeding cycle in trees. In this study, 390 trees from 74 control-pollinated families were genotyped using a 36K Axiom SNP array. A total of 15,624 high-quality SNPs were used to develop genomic prediction models for mammalian bark stripping, tree height, and selected primary and secondary chemical compounds in the bark. Genetic parameters from different genomic prediction methods-single-trait best linear unbiased prediction based on a marker-based relationship matrix (genomic best linear unbiased prediction), multitrait single-step genomic best linear unbiased prediction, which integrated the marker-based and pedigree-based relationship matrices (single-step genomic best linear unbiased prediction) and the single-trait generalized ridge regression-were compared to equivalent single- or multitrait pedigree-based approaches (ABLUP). The influence of the statistical distribution of data on the genetic parameters was assessed. Results indicated that the heritability estimates were increased nearly 2-fold with genomic models compared to the equivalent pedigree-based models. Predictive accuracy of the single-step genomic best linear unbiased prediction was higher than the ABLUP for most traits. Allowing for heterogeneity in marker effects through the use of generalized ridge regression did not markedly improve predictive ability over genomic best linear unbiased prediction, arguing that most of the chemical traits are modulated by many genes with small effects. Overall, the traits with low pedigree-based heritability benefited more from genomic models compared to the traits with high pedigree-based heritability. There was no evidence that data skewness or the presence of outliers affected the genomic or pedigree-based genetic estimates.

A multi-omics framework reveals strawberry flavor genes and their regulatory elements.

Flavor is essential to consumer preference of foods and is an increasing focus of plant breeding programs. In fruit crops, identifying genes underlying volatile organic compounds has great promise to accelerate flavor improvement, but polyploidy and heterozygosity in many species have slowed progress. Here we use octoploid cultivated strawberry to demonstrate how genomic heterozygosity, transcriptomic intricacy and fruit metabolomic diversity can be treated as strengths and leveraged to uncover fruit flavor genes and their regulatory elements. Multi-omics datasets were generated including an expression quantitative trait loci map with 196 diverse breeding lines, haplotype-phased genomes of a highly-flavored breeding selection, a genome-wide structural variant map using five haplotypes, and volatile genome-wide association study (GWAS) with > 300 individuals. Overlaying regulatory elements, structural variants and GWAS-linked allele-specific expression of numerous genes to variation in volatile compounds important to flavor. In one example, the functional role of anthranilate synthase alpha subunit 1 in methyl anthranilate biosynthesis was supported via fruit transient gene expression assays. These results demonstrate a framework for flavor gene discovery in fruit crops and a pathway to molecular breeding of cultivars with complex and desirable flavor.

Integrating genomic information and productivity and climate-adaptability traits into a regional white spruce breeding program.

Tree improvement programs often focus on improving productivity-related traits; however, under present climate change scenarios, climate change-related (adaptive) traits should also be incorporated into such programs. Therefore, quantifying the genetic variation and correlations among productivity and adaptability traits, and the importance of genotype by environment interactions, including defense compounds involved in biotic and abiotic resistance, is essential for selecting parents for the production of resilient and sustainable forests. Here, we estimated quantitative genetic parameters for 15 growth, wood quality, drought resilience, and monoterpene traits for Picea glauca (Moench) Voss (white spruce). We sampled 1,540 trees from three open-pollinated progeny trials, genotyped with 467,224 SNP markers using genotyping-by-sequencing (GBS). We used the pedigree and SNP information to calculate, respectively, the average numerator and genomic relationship matrices, and univariate and multivariate individual-tree models to obtain estimates of (co)variance components. With few site-specific exceptions, all traits examined were under genetic control. Overall, higher heritability estimates were derived from the genomic- than their counterpart pedigree-based relationship matrix. Selection for height, generally, improved diameter and water use efficiency, but decreased wood density, microfibril angle, and drought resistance. Genome-based correlations between traits reaffirmed the pedigree-based correlations for most trait pairs. High and positive genetic correlations between sites were observed (average 0.68), except for those pairs involving the highest elevation, warmer, and moister site, specifically for growth and microfibril angle. These results illustrate the advantage of using genomic information jointly with productivity and adaptability traits, and defense compounds to enhance tree breeding selection for changing climate.

High male specific contribution of the X-chromosome to individual global recombination rate in dairy cattle

BackgroundMeiotic recombination plays an important role in reproduction and evolution. The individual global recombination rate (GRR), measured as the number of crossovers (CO) per gametes, is a complex trait that has been shown to be heritable. The sex chromosomes play an important role in reproduction and fertility related traits. Therefore, variants present on the X-chromosome might have a high contribution to the genetic variation of GRR that is related to meiosis and to reproduction.ResultsWe herein used genotyping data from 58,474 New Zealand dairy cattle to estimate the contribution of the X-chromosome to male and female GRR levels. Based on the pedigree-based relationships, we first estimated that the X-chromosome accounted for 30% of the total additive genetic variance for male GRR. This percentage was equal to 19.9% when the estimation relied on a SNP-BLUP approach assuming each SNP has a small contribution. We then carried out a haplotype-based association study to map X-linked QTL, and subsequently fine-mapped the identified QTL with imputed sequence variants. With this approach we identified three QTL with large effect accounting for 7.7% of the additive genetic variance of male GRR. The associated effects were equal to + 0.79, − 1.16 and + 1.18 CO for the alternate alleles. In females, the estimated contribution of the X-chromosome to GRR was null and no significant association with X-linked loci was found. Interestingly, two of the male GRR QTL were associated with candidate genes preferentially expressed in testis, in agreement with a male-specific effect. Finally, the most significant QTL was associated with PPP4R3C, further supporting the important role of protein phosphatase in double-strand break repair by homologous recombination.ConclusionsOur study illustrates the important role the X-chromosome can have on traits such as individual recombination rate, associated with testis in males. We also show that contribution of the X-chromosome to such a trait might be sex dependent.

A Random Regression Model Based on a Single-Step Method for Improving the Genomic Prediction Accuracy of Residual Feed Intake in Pigs.

Residual feed intake (RFI) is considered as a measurement of feed efficiency, which is greatly related to the growth performance in pigs. Daily feeding records can be obtained from automatic feeders. In general, RFI is usually calculated from the total measurement records during the whole test period. This measurement cannot reflect genetic changes in different growth periods during the test. A random regression model (RRM) provides a method to model such type of longitudinal data. To improve the accuracy of genetic prediction for RFI, the RRM and regular animal models were applied in this study, and their prediction performances were compared. Both traditional pedigree-based relationship matrix (A matrix) and pedigree and genomic information-based relationship matrix (H matrix) were applied for these two models. The results showed that, the prediction accuracy of the RRM was higher than that of the animal model, increasing 24.2% with A matrix and 40.9% with H matrix. Furthermore, genomic information constantly improved the accuracy of evaluation under each evaluation model. In conclusion, longitudinal traits such as RFI can describe feed efficiency better, and the RRM with both pedigree and genetic information was superior to the animal model. These results provide a feasible method of genomic prediction using longitudinal data in animal breeding.

Single-Step Genomic Analysis Increases the Accuracy of Within-Family Selection in a Clonally Replicated Population ofPinus taedaL.

AbstractThe use of genomic markers in forest tree breeding is expected to improve the response to selection, especially within family. To evaluate the potential improvements from genotyping, we analyzed a large Pinus taeda L. clonal population (1,831 cloned individuals) tested in multiple environments. Of the total, 723 clones from five full-sib families were genotyped using 10,337 single-nucleotide polymorphism markers. Single-step models with genomic and pedigree-based relationships produced similar heritability estimates. Breeding value predictions were greatly improved with inclusion of genomic relationships, even when clonal replication was abundant. The improvement was limited to genotyped individuals and attributable to accounting for the Mendelian sampling effect. Reducing clonal replication by omitting data indicated that genotyping improved breeding values similar to clonal replication. Genomic selection predictive ability (masking phenotypes) was greater for stem straightness (0.68) than for growth traits (0.41 to 0.44). Predictive ability for a new full-sibling family was poorer than when full-sibling relationships were present between model training and validation sets. Species that are difficult to propagate clonally can use genotyping to improve within-family selection. Clonal testing combined with genotyping can produce breeding value accuracies adequate to graft selections directly into deployment orchards without progeny testing.

Estimating heritability of glycaemic response to metformin using nationwide electronic health records and population-sized pedigree

BackgroundVariability of response to medication is a well-known phenomenon, determined by both environmental and genetic factors. Understanding the heritable component of the response to medication is of great interest but challenging due to several reasons, including small study cohorts and computational limitations.MethodsHere, we study the heritability of variation in the glycaemic response to metformin, first-line therapeutic agent for type 2 diabetes (T2D), by leveraging 18 years of electronic health records (EHR) data from Israel’s largest healthcare service provider, consisting of over five million patients of diverse ethnicities and socio-economic background. Our cohort consists of 80,788 T2D patients treated with metformin, with an accumulated number of 1,611,591 HbA1C measurements and 4,581,097 metformin prescriptions. We estimate the explained variance of glycated hemoglobin (HbA1c%) reduction due to inheritance by constructing a six-generation population-size pedigree from national registries and linking it to medical health records.ResultsUsing Linear Mixed Model-based framework, a common-practice method for heritability estimation, we calculate a heritability measure of {h}^{2}=12.6 % (95% CI, 6.1 %! -!19.1 %) for absolute reduction of HbA1c% after metformin treatment in the entire cohort, {h}^{2}=21.0 % (95% CI, 7.8 %! -!34.4 %) for males and {h}^{2}=22.9 % (95% CI, 10.0 %! -!35.7 %) in females. Results remain unchanged after adjusting for pre-treatment HbA1c%, and in proportional reduction of HbA1c%.ConclusionsTo the best of our knowledge, our work is the first to estimate heritability of drug response using solely EHR data combining a pedigree-based kinship matrix. We demonstrate that while response to metformin treatment has a heritable component, most of the variation is likely due to other factors, further motivating non-genetic analyses aimed at unraveling metformin’s action mechanism.

Enhanced stripe rust resistance obtained by combining Yr30 with a widely dispersed, consistent QTL on chromosome arm 4BL.

YrFDC12 and PbcFDC, co-segregated in chromosome 4BL, and significantly interacted with Yr30/Pbc1 to enhance stripe rust resistance and to promote pseudo-black chaff development. Cultivars with durable resistance are the most popular means to control wheat stripe rust. Durable resistance can be achieved by stacking multiple adult plant resistance (APR) genes that individually have relatively small effect. Chinese wheat cultivars Ruihua 520 (RH520) and Fengdecun 12 (FDC12) confer partial APR to stripe rust across environments. One hundred and seventy recombinant inbred lines from the cross RH520 × FDC12 were used to determine the genetic basis of resistance and identify genomic regions associated with stripe rust resistance. Genotyping was carried out using 55K SNP array, and eight quantitative trait loci (QTL) were detected on chromosome arms 2AL, 2DS, 3BS, 4BL, 5BL (2), and 7BL (2) by inclusive composite interval mapping. Only QYr.nwafu-3BS from RH520 and QYr.nwafu-4BL.2 (named YrFDC12 for convenience) from FDC12 were consistent across the four testing environments. QYr.nwafu-3BS is likely the pleiotropic resistance gene Sr2/Yr30. YrFDC12 was mapped in a 2.1-cM interval corresponding to 12Mb and flanked by SNP markers AX-111121224 and AX-89518393. Lines harboring both Yr30 and YrFDC12 displayed higher resistance than the parents and expressed pseudo-black chaff (PBC) controlled by loci Pbc1 and PbcFDC12, which co-segregated with Yr30 and YrFDC12, respectively. Both marker-based and pedigree-based kinship analyses revealed that YrFDC12 was inherited from founder parent Zhou 8425B. Fifty-four other wheat cultivars shared the YrFDC12 haplotype. These results suggest an effective pyramiding strategy to acquire highly effective, durable stripe rust resistance in breeding.

16Years of breed management brings substantial improvement in population genetics of the endangered Cleveland Bay Horse.

The consequences of poor breed management and inbreeding can range from gradual declines in individual productivity to more serious fertility and mortality concerns. However, many small and closed groups, as well as larger unmanaged populations, are plagued by genetic regression, often due to a dearth in breeding support tools which are accessible and easy to use in supporting decision‐making. To address this, we have developed a population management tool (BCAS, Breed Conservation and Management System) based on individual relatedness assessed using pedigree‐based kinship, which offers breeding recommendations for such populations. Moreover, we demonstrate the success of this tool in 16 years of employment in a closed equine population native to the UK, most notably, the rate of inbreeding reducing from more than 3% per generation, to less than 0.5%, or that attributed to genetic drift, as assessed over the last 16 years of implementation. Furthermore, with adherence to this program, the long‐term impact of poor management has been reversed and the genetic resource within the breed has grown from an effective population size of 20 in 1994 to more than 140 in 2020. The development and availability of our BCAS for breed management and selection establish a new paradigm for the successful maintenance of genetic resources in animal populations.