Biology subjects

Thelen, K.

Publications and source records attributed to Thelen, K..

4 recordsLinked to original sources

bioRxiv2025

An Axiom SNP genotyping array for potato: development, evaluation and applications

Potato is a versatile food crop and a major component of human nutrition worldwide. Genomic-assisted breeding methods have the potential to increase the gain of selection. We report the development and validation of a high-density Axiom-based SNP array for potato (Solanum tuberosum L.). Whole-genome 10X Genomics based sequencing of 108 diverse clones representing landraces, improved cultivars, and wild relatives identified around 23.8 million sequence variants, from which 929,127 variants, alongside with 18,718 markers from a previously developed Illumina Infinium 21K array (GGP3), were tiled on the array. The array demonstrated high reproducibility, with replicate samples showing an average concordance of 99.88% in genotype calls for PotatoTools specific variants, compared to 99.93% for the Illumina Infinium 21K array variants. A panel of 1,247 diploid and tetraploid clones was genotyped with the developed array. Genotype calling, considering allele dosage, was realized using fitpoly and yielded 852,793 calls. The array informativeness was optimized by applying Euclidean distance, heterozygous strength offset metrics, call rate, minor allele frequency filtering, and diploid-based allele correction, yielding a final set of 206,616 robust and informative markers. The filtered marker set enables precise characterization of genetic variation across diverse germplasm, thereby supporting robust analyses of population structure, genome-wide association studies (GWAS), and genomic prediction in potato. Population structure analysis genotyped clones revealed clear subpopulation differentiation consistent with known ploidy groups. In addition, our discriminant analysis of principal components revealed a weak but structured diversity among clones of different market segments. GWAS analysis of 998 potato clones identified sequence variants significantly associated with polyphenol oxidase (PPO) activity, confirming the platforms efficacy for trait mapping. For the same trait, genomic prediction accuracies of 0.72-0.86 have been observed. The developed potato SNP array provides a robust platform for high-throughput genotyping, supporting genetic diversity studies, association mapping, and genomic-assisted breeding in this important crop.

plant biology↗

bioRxiv2025

Assessment of segregation variance estimates from derivation, simulations, and empirical data in autotetraploid species exemplified in potato

The optimal choice of parents and crosses and, therefore, the prediction of the segregation variance are of high relevance to maximize genetic gain in breeding programs. Several methods have been developed for the prediction of segregation variance, including correlation with genotypic diversity, progeny simulations, or algebraic derivations in case of a diploid inheritance. To the best of our knowledge, no algebraic derivation using parental genotypic information is available to predict segregation variance for autotetraploid species. The objectives of our study were to (1) derive algebraic derivation based on linkage disequilibrium (LD) between linked loci to predict the segregation variance in autotetraploid species; (2) compare the performance of segregation variance estimated based on simulated progenies and the algebraic derivation; (3) investigate by simulations how experimental parameters affect the accuracy of segregation variance prediction; and (4) compare the segregation variance estimated in empirical data of potato and the one based on the algebraic derivation. The segregation variance estimated by the developed derivations showed very high correlations with the one observed in large simulated progenies, but those were lower when phased parental haplotypes were not available or family size decreased. The correlation between segregation variance estimated by the developed derivation and the empirical data was low. This could be attributed to the small family size used in the study, which we could show to increase LD between unlinked loci. The proposed algebraic derivations promise to be a precise alternative to simulations to help breeders in optimizing their family choices and sizes considering the segregation variance.

genetics↗

bioRxiv2024

Activity-dependent FosB gene expression negatively regulates mast cell functions.

Mast cells are innate immune cells that regulate physiological processes by releasing pre-stored and newly synthesized mediators in response to allergens, infection, and other stimuli. Dysregulated mast cell activity can lead to multisystemic pathologies, but the underlying regulatory mechanisms remain poorly understood. We found that FOSB and {Delta}FOSB, transcription factors encoded by the FosB gene, are robustly expressed in mast cells following IgE-antigen stimulation, suggesting a role in modulating stimulus-induced mast cell functions. Using phenotypic, gene binding, and gene expression analyses in wild-type and mast cell-specific FosB knockout male mice, we demonstrate that FOSB/{Delta}FOSB modulates mast cell functions by limiting reactivity to allergen-like stimuli both in vitro and in vivo. These effects seem to be mediated, at least in part, by FOSB/{Delta}FOSB-driven enhanced expression of DUSP4, a dual-specificity phosphatase that attenuates MAPK signaling. These findings highlight FOSB/{Delta}FOSB as critical regulators of mast cell activity and potential targets for therapeutic intervention. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/592755v2_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@190be2corg.highwire.dtl.DTLVardef@1b53f9borg.highwire.dtl.DTLVardef@631997org.highwire.dtl.DTLVardef@250bc7_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Effects of early life adversity on meningeal mast cells and proinflammatory gene expression in male and female Mus musculus

Exposure to early life adversity (ELA) in the form of physical and/or psychological abuse or neglect increases the risk of developing psychiatric and inflammatory disorders later in life. It has been hypothesized that exposure to ELA results in persistent, low grade inflammation that leads to increased disease susceptibility by amplifying the crosstalk between stress-processing brain networks and the immune system, but the mechanisms remain largely unexplored. The meninges, a layer of three overlapping membranes that surround the central nervous system (CNS)- duramater, arachnoid, and piamater - possess unique features that allow them to play a key role in coordinating immune trafficking between the brain and the peripheral immune system. These include a network of lymphatic vessels that carry cerebrospinal fluid from the brain to the deep cervical lymph nodes, fenestrated blood vessels that allow the passage of molecules from blood to the CNS, and a rich population of resident mast cells, master regulators of the immune system. Using a mouse model of ELA consisting of neonatal maternal separation plus early weaning (NMSEW), we sought to explore the effects of ELA on duramater mast cell histology and expression of inflammatory markers in male and female C57Bl/6 mice. We found that mast cell number, activation level, and relative expression of pseudopodia differ across duramater regions, and that NMSEW exerts region-specific effects on mast cells in males and females. Using gene expression analyses, we next found that NMSEW increases the expression of inflammatory markers in the duramater of females but not males, and that this is prevented by pharmacological inhibition of mast cells with ketotifen. Together, our results show that ELA drives sex-specific, long-lasting effects on the duramater mast cell population and immune-related gene expression, suggesting that the long-lasting effects of ELA on disease susceptibility could be partly mediated by meningeal function.

immunology↗