Biology subjects

Pocrnic, I.

Publications and source records attributed to Pocrnic, I..

12 recordsLinked to original sources

bioRxiv2025

Review: Estimates of livestock genetic diversity in the UK

The United Kingdom is home to many local and rare livestock breeds. The local breed populations are highly adapted to specific environments in the United Kingdom and these and other rare breeds provide solutions to niche needs. Rare breeds often contribute more than expected to overall species genetic diversity, which is important because genetic variation is needed for adapting to new challenges. It is therefore very important from both United Kingdom and global perspectives to maintain genetic diversity of rare livestock breeds in the United Kingdom, and to do this, we need to evaluate the monitoring of genetic diversity to identify gaps in our knowledge and prioritise resources reserved for conservation purposes. The objectives of this study were to survey the literature to: (1) summarise genetic/genomic characterisation (effective population size (Ne) and inbreeding) of domestic populations (livestock and equine) in the United Kingdom and Ireland; (2) compare number of populations on the United Kingdoms Rare Breeds Survival Trust watch list and the number of United Kingdom and Irish populations in the peer-reviewed literature with inbreeding, genetic diversity and/or Ne estimates; and (3) compare annually reported (census-based) estimates of Ne with (inbreeding- and DNA-based) estimates from peer-reviewed literature. We found a total of 37 publications with Ne or inbreeding estimates for United Kingdom or Ireland livestock populations, published from 1975 to 2024. While many (42%) of the breeds on the Rare Breeds Survival Trust watchlist have been included in publications, there are still many breeds, and a few species (turkey, duck and geese) with no publicly available pedigree- or DNA-based genetic diversity measures. We found census-based Ne estimates were, on average, higher than DNA-based estimates, likely due to violated assumptions when estimating Ne with census-based data because of the way livestock mating systems are designed. Most peer-reviewed papers estimated genetic diversity measures using pedigree, microsatellite markers, or single nucleotide polymorphisms (SNP) markers. To identify breed-unique variants responsible for adaptive traits in rare breeds, more studies using whole-genome sequencing will be needed. Altogether, we have summarised genetic diversity estimates of United Kingdom livestock populations, identifying gaps in knowledge. ImplicationsMaintaining genetic diversity in livestock helps safeguard against future challenges to our food production systems. We surveyed publicly available measures of genetic diversity for farm animal populations in the United Kingdom (including government, Rare Breeds Survival Trust, and peer-reviewed scientific publications) to identify any gaps. We found census-based estimates of genetic diversity, which are used to inform and prioritise resources for conservation efforts, on average, are likely overestimating available genetic diversity. Additionally, most farm animal breeds had only these census-based estimates. Genetic diversity estimates could be improved using pedigree or DNA information, more accurately identifying endangered breeds.

genetics↗

bioRxiv2025

Spatial modelling improves genomic evaluation in Tanzanian smallholder admixed dairy cattle

BackgroundSmallholder dairy production systems in low-and middle-income countries are characterised by large phenotypic variance due to diverse environmental effects, farming practices, and crossbreeding. Furthermore, small herds, low genetic connectedness, and limited data recording challenge accurate separation of environmental and genetic effect in such settings, limiting genetic improvement. Here, we evaluated the impact of modelling spatial variation between herds to address these challenges and improve the accuracy of genomic evaluation for Tanzanian smallholder dairy cattle. ResultsWe analysed 19,375 test-day milk yield records of 1894 dairy cows from 1386 herds across four distinct geographical regions in Tanzania. The cows had 664,822 SNP marker genotypes after quality control and were highly admixed. We fitted a series of GBLUP models to evaluate the impact of modelling the herd effect and the spatial effect on. The herd effect was fitted as an independent random effect, while the spatial effect was fitted as a random effect with Euclidean distance-based Matern covariance function. The models were compared based on: model fit; estimates of variance components and breeding values; correlations between the estimated contribution of breeding values, herd effect, and spatial effect to phenotype values; and the accuracy of phenotype prediction in cross-validation and forward validation. The results showed large differences in milk yield between and within regions, as well as significant variation due to the spatial effect, which were not fully captured by modelling the herd effect. The results also strongly indicate that a model with just the herd effect underestimated breeding values of animals in less favourable environments and overestimated breeding values of animals in more favourable environments. ConclusionsThis study demonstrated the challenge of achieving accurate genomic evaluation in smallholder settings. By leveraging spatial modelling we maximised the use of available data and improved the separation of genetic and environmental effects. Further work is required to improve smallholder genetic evaluations by understanding environmental and genetic processes that drive the large phenotypic variance in African smallholder setting.

genomics↗

bioRxiv2024

Unlocking genome-based prediction and selection in conifers: the key role of within-family prediction accuracy

ContextGenomic selection is a promising approach for forest tree breeding. However, its advantage in terms of prediction accuracy over conventional pedigree-based methods is unclear and within-family accuracy is rarely assessed. AimsWe used an pedigree-based model (ABLUP) with corrected pedigree data as a baseline reference for assessing the prediction accuracy of genome-based model (GBLUP) at the global and within-family levels in maritime pine (Pinus pinaster Ait). MethodsWe sampled 39 full-sib families, each comprising 10 to 40 individuals, to constitute an experimental population of 833 individuals. A stochastic simulation model was also developed to explore other scenarios of heritability, training set size and tagging density. ResultsPrediction accuracies with GBLUP and ABLUP were similar and accuracy with GBLUP within-family was on average zero with large variation between families. Simulations revealed that the number of individuals in the training set was the principal factor limiting GBLUP accuracy in our study and likely in many forest tree breeding programmes. Accurate within-family prediction is possible if 40-65 individuals per full-sib family are included in the genomic training set, from a total of 1600-2000 individuals in the training set. ConclusionSuch conditions lead to a significant advantage of GBLUP over ABLUP in terms of prediction accuracy and more clearly justify the switch to genome-based prediction and selection in forest trees.

genomics↗

bioRxiv2023

Accounting for nuclear and mito genome in dairy cattle breeding - a simulation study

Mitochondria play a significant role in numerous cellular processes through proteins encoded by both nuclear genome (nDNA) and mito genome (mDNA). While the variation in nDNA is influenced by mutations and recombination of parental genomes, the variation in mDNA is solely driven by mutations. In addition, mDNA is inherited in a haploid form, from the dam. Cattle populations show significant variation in mDNA between and within breeds. Past research suggests that variation in mDNA accounts for 1-5% of the phenotypic variation in dairy traits. Here we simulated a dairy cattle breeding program to assess the impact of accounting for mDNA variation in pedigree-based and genome-based genetic evaluations on the accuracy of estimated breeding values for mDNA and nDNA components. We also examined the impact of alternative definitions of breeding values on genetic gain, including nDNA and mDNA components that both impact phenotype expression, but mDNA is inherited only maternally. We found that accounting for mDNA variation increased accuracy between +0.01 and +0.05 for different categories of animals, especially for young bulls (+0.05) and females without genotype data (between +0.01 and +0.03). Different scenarios of modelling and breeding value definition impacted genetic gain. The standard approach of ignoring mDNA variation achieved competitive genetic gain. Modelling, but not selecting on mDNA expectedly reduced genetic gain, while optimal use of mDNA variation recovered the genetic gain.

genetics↗

bioRxiv2023

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{degrees} and 65{degrees}. 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.

genetics↗

bioRxiv2023

SNP profile for quantitative trait nucleotide in populations with small effective size and its impact on mapping and genomic predictions

In animal populations, increasing the SNP density by incorporating sequence information only marginally increases prediction accuracies. To find out why, we used statistical models and simulations to investigate the profile or distribution of SNP around Quantitative Trait Nucleotides (QTN) in populations with small effective population size (Ne). A QTN profile created by averaging SNP solutions around each QTN was similar to the shape of expected pairwise linkage disequilibrium (PLD) based on Ne and genetic distance between SNP, with a distinct peak for the QTN. Populations with smaller Ne showed lower but wider QTN profiles; however, adding more genotyped individuals with phenotypes dragged the profile closer to the QTN; the QTN profile was higher and narrower for populations with larger compared to smaller Ne. Assuming the PLD curve for the QTN profile, 80% of the additive genetic variance explained by each QTN is contained in 8 "Stam" segments (one segment = 1/4Ne Morgans), corresponding to 1.6 Mb in cattle, and 5 Mb in pigs and broiler chickens. With such large segments, identifying QTN is difficult even if all of them are in the data and the assumed genetic architecture is simplistic. Additional complexity in QTN detection arises from confounding of QTN profiles with signals due to relationships, overlapping profiles with closely-spaced QTN, and spurious signals due to imputation errors. However, small Ne allows for accurate prediction with large data even without QTN identification because QTN are accounted for by QTN profiles if SNP density is sufficient to saturate the segments.

genetics↗

bioRxiv2022

The benefits and perils of import in small cattle breeding programs

Small breeding programs are limited in achieving competitive genetic gain and prone to high rates of inbreeding. Thus, they often import genetic material to increase genetic gain and to limit the loss of genetic variability. However, the benefit of import depends on the strength of genotype by environment interaction. It also also diminishes the relevance of domestic selection and the use of domestic breeding animals. Introduction of genomic selection has potentially execerbated this issue, but is also opening the potential for smaller breeding program. The aim of this paper was to determine when and to what extent do small breeding programs benefit from import. We simulated two cattle breeding programs differing in selection parameters representing a large foreign and a small domestic breeding program that differ in the initial genetic mean and annual genetic gain. We evaluated a control scenario without the use of foreign sires in the domestic breeding program and 20 scenarios that varied the percentage of domestic dams mated with foreign sires, the genetic correlation between the breeding programs (0.8 or 0.9), and the time of implementing genomic selection in the domestic compared to the foreign breeding program (concurrently or with a 10-year delay). We compared the scenarios based on the genetic gain and genic standard deviation. Finally, we partitioned breeding values and genetic trends of the scenarios to quantify the contribution of domestic selection and import to the domestic genetic gain. The simulation revealed that when both breeding programs implemented genomic selection simultaneously, the use of foreign sires increased domestic genetic gain only when genetic correlation was 0.9. In contrast, when the domestic breeding program implemented genomic selection with a 10-year delay, genetic correlation of 0.8 sufficed for a positive impact of import. In that scenario, domestic genetic gain increased with the increasing use of foreign sires but with a diminishing return. The partitioning analysis revealed that the contribution of import expectedly increased with the increased use of foreign sires. However, the increase did not depend on the genetic correlation and was not proportional to the increase in domestic genetic gain. This means that a small breeding program could be overly relying on import with diminishing returns for the genetic gain and marginal benefit for the genetic variability. The benefit of import depends on an interplay of genetic correlation, extent of using foreign sires, and a breeding scheme. It is therefore crucial that small breeding programs assess the possible benefits of import beyond domestic selection. The benefit of import should be weighted against the perils of decreased use of domestic sires and decreased contribution and value of domestic selection.

genetics↗

bioRxiv2022

Optimisation of the core subset for the APY approximation of genomic relationships

BackgroundBy entering the era of mega-scale genomics, we are facing many computational issues with standard genomic evaluation models due to their dense data structure and cubic computational complexity. Several scalable approaches have have been proposed to address this challenge, like the Algorithm for Proven and Young (APY). In APY, genotyped animals are partitioned into core and non-core subsets, which induces a sparser inverse of genomic relationship matrix. The partitioning into subsets is often done at random. While APY is a good approximation of the full model, the random partitioning can make results unstable, possibly affecting accuracy or even reranking animals. Here we present a stable optimisation of the core subset by choosing animals with the most informative genotype data. MethodsWe derived a novel algorithm for optimising the core subset based on the conditional genomic relationship matrix or the conditional SNP genotype matrix. We compared accuracy of genomic predictions with different core subsets on simulated and real pig data. The core subsets were constructed (1) at random, (2) based on the diagonal of genomic relationship matrix, (3) at random with weights from (2), or (4) based on the novel conditional algorithm. To understand the different core subset constructions, we have visualised population structure of genotyped animals with the linear Principal Component Analysis and the non-linear Uniform Manifold Approximation and Projection. ResultsAll core subset constructions performed equally well when the number of core animals captured most of variation in genomic relationships, both in simulated and real data. When the number of core animals was not optimal, there was substantial variability in results with the random construction and no variability with the conditional construction. Visualisation of population structure and chosen core animals showed that the conditional construction spreads core animals across the whole domain of genotyped animals in a repeatable manner. ConclusionsOur results confirm that the size of the core subset in APY is critical. The results further show that the core subset can be optimised with the conditional algorithm that achieves a good and repeatable spread of core animals across the domain of genotyped animals.

genetics↗

bioRxiv2022

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

BackgroundIn breeding programmes, the observed genetic change is a sum of the contributions of different 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 groups 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. MethodsWe first extended the partitioning method to quantify the contribution of different groups to genetic variance assuming 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. ResultsWe showed how to quantify the contribution of different groups of individuals to genetic mean and variance. We showed that the contributions of different selection paths to genetic variance are not necessarily independent. Finally, we observed some limitations of the partitioning method under a misspecified model, suggesting the need for a genomic partitioning method. ConclusionWe 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 paths of selection interact within a breeding programme and how they can be optimised.

genetics↗

bioRxiv2020

Temporal and genomic analysis of additive genetic variance in breeding programmes

This study demonstrates a framework for temporal and genomic analysis of additive genetic variance in a breeding programme. Traditionally we used specific experimental designs to estimate genetic variance for a specific group of individuals and a general pedigree-based model to estimate genetic variance for pedigree founders. However, with the pedigree-based model we can also analyse temporal changes in genetic variance by summarising sampled realisations of genetic values from a fitted model. Here we extend this analysis to a marker-based model and build a framework for temporal and genomic analyses of genetic variance. The framework involves three steps: (i) fitting a marker-based model to data, (ii) sampling realisations of marker effects from the fitted model and for each sample calculating realisations of genetic values, and (iii) calculating variance of the sampled genetic values by time and genome partitions. Genome partitions enable estimation of contributions from chromosomes and chromosome pairs and genic and linkage-disequilibrium variances. We demonstrate the framework by analysing data from a simulated breeding programme involving a complex trait with additive gene action. We use the full Bayesian and empirical Bayesian approaches to account for the uncertainty due to model fitting. We also evaluate the use of principal component approximation. Results show good concordance between the simulated and estimated variances for temporal and genomic analyses and give insight into genetic processes. For example, we observe reduction of genic variance due to selection and drift and buildup of negative linkage-disequilibrium (the Bulmer effect) due to directional selection. In this study the popular empirical Bayesian approach estimated the variances well but it underestimated uncertainty of the estimates. The principal components approximation biases estimates, in particular for the genic variance. This study gives breeders a framework to analyse genetic variance and its components in different stages of a programme and over time.

genetics↗

bioRxiv2020

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread

Invasive species are among the major driving forces behind biodiversity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR can effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.

genetics↗

bioRxiv2016

Metafounders are Fst fixation indices and reduce bias in single step genomic evaluations

BACKGROUNDMetafounders are pseudo-individuals that condense the genetic heterozygosity and relationships within and across base pedigree populations, i.e. ancestral populations. This work addresses estimation and usefulness of metafounder relationships in Single Step GBLUP.\n\nRESULTSWe show that the ancestral relationship parameters are proportional to standardized covariances of base allelic frequencies across populations, like Fst fixation indexes. These covariances of base allelic frequencies can be estimated from marker genotypes of related recent individuals, and pedigree. Simple methods for estimation include naive computation of allele frequencies from marker genotypes or a method of moments equating average pedigree-based and marker-based relationships. Complex methods include generalized least squares or maximum likelihood based on pedigree relationships. To our knowledge, methods to infer Fst coefficients and Fst differentiation have not been developed for related populations.\n\nA compatible genomic relationship matrix constructed as a crossproduct of {-1,0,1} codes, and equivalent (up to scale factors) to an identity by state relationship matrix at the markers, is derived. Using a simulation with a single population under selection, in which only males and youngest animals were genotyped, we observed that generalized least squares or maximum likelihood gave accurate and unbiased estimates of the ancestral relationship parameter (true value: 0.40) whereas the other two (naive and method of moments) were biased (estimates of 0.43 and 0.35). We also observed that genomic evaluation by Single Step GBLUP using metafounders was less biased in terms of accurate genetic trend (0.01 instead of 0.12 bias), slightly overdispersed (0.94 instead of 0.99) and as accurate (0.74) than the regular Single Step GBLUP. Single Step GBLUP using metafounders also provided consistent estimates of heritability.\n\nCONCLUSIONSEstimation of metafounder relationship can be achieved using BLUP-like methods with pedigree and markers. Inclusion of metafounder relationships improves bias of genomic predictions with no loss in accuracy.

genetics↗