Biology subjects

Jensen, C. S.

Publications and source records attributed to Jensen, C. S..

4 recordsLinked to original sources

bioRxiv2026

Genomic prediction of single cross families of perennial ryegrass in two nitrogen managements

The performance of a single cross is determined by the average additive effects of the parents, as well as the interactions between them. These quantities can be estimated using an appropriate genetic design, allowing for the estimation of general (GCA) and specific (SCA) combining abilities. The prediction of GCA for new parents and the total genetic value of unrealized crosses can be made when genome-wide marker information is available. Several studies in crops such as maize and rice have demonstrated the potential of genomic-assisted prediction of single-cross performance in economically important crops. However, no study to date has explored its relevance in perennial ryegrass, an obligate allogamous species that is bred in genetically heterogeneous families. In this study, we aimed to estimate genetic parameters and assess the ability of genomic models to predict the performance of F2 families in terms of dry matter yield and nutritive quality traits. We used data from a large partial diallel involving 104 parents from two distinct subpopulations, as inferred by admixture analysis. F2 families were evaluated in multiple environments and under two nitrogen availability conditions. Genotyping-by-sequencing of the parent plants produced 42,145 variants after quality control, which were used to estimate genomic relationships based on identity-by-state. Variance component estimation revealed limited GCA and SCA interactions with the environment, and particularly with nitrogen management. The predictive abilities of two parental models exceeded 0.60 and often surpassed 0.70 for most traits. However, incorporating non-additive effects into the model did not improve predictive ability. We leveraged the genetic diversity among parents to map genomic regions associated with all recorded traits. Genome-wide association studies (GWAS) by genomic best linear unbiased prediction (GBLUP) identified six quantitative trait loci (QTL) regions, with 45 candidate genes within the linkage disequilibrium range, estimated at approximately 92 kb. Our results demonstrate that genomic prediction of single crosses can be performed with high accuracy, especially when both parents are also progenitors of families in the training set.

genomics↗

bioRxiv2025

Transferrin receptor-binding blood-brain barrier shuttle enhances brain delivery and efficacy of a therapeutic anti-Abeta antibody

Transferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. We sought to investigate brain delivery and efficacy of Aducanumab (Adu), an anti-A{beta} antibody, when fused to a mouse TfR1-binding Fab fragment as BBB shuttle (TfR1-Adu). Automated 3D light sheet fluorescence imaging coupled with computational analysis was applied to evaluate drug IgG distribution and plaque counts throughout the intact brain of transgenic APP/PS1 mice. TfR1-Adu demonstrated enhanced brain delivery and more homogeneous distribution after both acute and chronic dosing in transgenic APP/PS1 mice compared with unmodified Adu. Also, importantly, only unmodified Adu showed perivascular labelling. While high-dose Adu promoted A{beta} plaque depletion in multiple brain regions, similar plaque-clearing efficacy was achieved with a five-fold lower dose of TfR1-Adu. Furthermore, low-dose TfR1-Adu demonstrated greater capacity to reduce congophilic plaque burden. Collectively, these observations strongly support the applicability of TfR1-enabled BBB shuttle strategies to improve brain delivery and plaque-clearing efficacy while mitigating the risk of vascular-associated amyloid-related imaging abnormalities (ARIA) adverse effects associated with current A{beta} immunotherapeutics.

neuroscience↗

bioRxiv2022

Genetic architecture of inter-specific and -generic grass hybrids by network analysis on multi-omics data

Understanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce. Therefore, this study aimed to combine multi-omics from grass hybrids by prioritizing omic features based on the reconstruction of interacting networks and assessing their relevance in explaining economically important phenotypes. Transcriptomic and NMR-based metabolomic data were used for sparse estimation via the fused graphical lasso, followed by modularity-based gene expression and metabolite-metabolite network reconstruction, node hub identification, omic-phenotype association via pairwise fitting of a multivariate genomic model, and machine learning-based prediction study. Analyses were jointly performed across two data sets composed of family pools of hybrid ryegrass (Lolium perenne x L. multiflorum) and Festulolium loliaceum (L. perenne x Festuca pratensis), whose phenotypes were recorded for eight traits in field trials across two European countries in 2020/21. Our results suggest substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizing L. perenne with another species within the genus relative to across genera. However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled. The use of the graphical lasso method for network reconstruction and identification of biological targets is discussed with an emphasis on forage grass breeding.

genetics↗

bioRxiv2022

Leveraging spatio-temporal genomic breeding value estimates of dry matter yield and herbage quality in ryegrass via random regression models

Joint modeling of correlated multi-environment and multi-harvest data of perennial crop species may offer advantages in prediction schemes and a better understanding of the underlying dynamics in space and time. The goal of the present study was to investigate the relevance of incorporating the longitudinal dimension of within-season multiple harvests of biomass yield and nutritive quality traits of forage perennial ryegrass (Lolium perenne L.) in a reaction norm model setup that additionally accounts for genotype-environment interactions. Genetic parameters and accuracy of genomic breeding value predictions were investigated by fitting three random regression (random coefficients) linear mixed models (gRRM) using Legendre polynomial functions to the data. All models accounted for heterogeneous residual variance and moving average-based spatial adjustments within environments. The plant material consisted of 381 bi-parental family pools and four check varieties of diploid perennial ryegrass evaluated in eight environments for biomass yield and nutritive quality traits. The longitudinal dimension of the data arose from multiple harvests performed four times annually. The specified design generated a total of 16,384 phenotypic data points for each trait. Genomic DNA sequencing was performed using DNA nanoball-based technology (DNBseq) and yielded 56,645 single nucleotide polymorphisms (SNPs) which were used to calculate the allele frequency-based genomic relationship matrix used in all genomic random regression models. Biomass yields estimated additive genetic variance and heritability values were higher in later harvests. The additive genetic correlations were moderate to low in early measurements and peaked at intermediates, with fairly stable values across the environmental gradient, except for the initial harvest data collection. This led to the conclusion that complex genotype-by-environment interaction (GxE) arises from spatial and temporal dimensions in the early season, with lower re-ranking trends thereafter. In general, modeling the temporal dimension with a second-order orthogonal polynomial in the reaction norm mixed model framework improved the accuracy of genomic estimated breeding value prediction for nutritive quality traits, but no gain in prediction accuracy was detected for dry matter yield. This study leverages the flexibility and usefulness of gRRM models for perennial ryegrass research and breeding and can be readily extended to other multi-harvest crops.

genetics↗