Biology subjects

Baud, A.

Publications and source records attributed to Baud, A..

12 recordsLinked to original sources

bioRxiv2026

Replication of Host St6galnac1-Microbiome Association Across Distinct Experimental Conditions in Heterogeneous Stock Rats

The gut microbiome is shaped by both environmental and host genetic factors. Identifying specific host loci is essential for understanding the heritability of microbiome-associated traits. The gene St6galnac1 encodes a sialyltransferase involved in mucin O-glycosylation. Tonnele et al. (2025) identified significant associations between a locus containing St6galnac1 gene, and the abundance of genus Paraprevotella using cecal samples collected from fasted animals. This association was replicated across three cohorts and paralleled with association found in humans between a functionally related sialyltransferase gene ST6GAL1 and Paraprevotella. Given the sensitivity of microbiome analyses to factors including sampling site, feeding status, and analytical framework, independent replication of these findings is important and it is also important to know if the association generalizes across other conditions or is highly specific to certain environments. Here, we performed a replication analysis using stool (not cecal) samples from 174 HS rats that were not fasted prior to collection. Stool samples underwent 16S rRNA gene sequencing, and microbial community structure was analyzed using compositionally aware methods. The rats were genotyped at the top SNP that was associated with Paraprevotella in the Tonnele et al. (2025) study. The association between genotype and Paraprevotella abundance was tested using a linear mixed model accounting for sex, cohort, and genetic relatedness. We successfully replicated (p=0.015) St6galnac1 - Paraprevotella association. These findings support the robustness of the St6galnac1 - Paraprevotella association across different sampling strategies and experimental conditions.

genomics↗

bioRxiv2026

Genetic backgrounds and sex modulate indirect genetic effects of Epha4 in laboratory mice

The phenotype of a focal individual can be affected not only by the individuals own genes (direct genetic effects, DGE) but also by genes of other individuals it interacts with (indirect genetic effects, IGE). Better understanding IGE can help better understand the impact and mechanisms of social effects. Here, we investigated, in laboratory mice, the modulation of IGE by genetic background of the focal individual (social epistasis) and by sex. We focused on IGE arising from Epha4, a gene that has been associated with the individuals own stress-related and social behaviours (i.e. DGE) and the stress-coping behaviour and wound healing of the other mice in the cage (i.e. IGE). Among four different genetic backgrounds for focal mice, significant IGE from Epha4 were detected in CBA females only. A formal model selection analysis was consistent with the modulation of IGE by the similarity of the genetic backgrounds of the focal mouse and its Epha4 cage mate, as well as by sex. Observations of fighting in cages of males with dissimilar genetic backgrounds suggested aggression might underpin these modulatory effects, which prompted to us to expand the conceptual framework describing the mechanisms of social epistasis. Thus, our results strengthen the emerging view that IGE are not fixed properties of social genotypes but can depend on the genetic and sex context of interacting individuals, revealing an underexplored layer of their genetic architecture.

genetics↗

bioRxiv2026

Phenome-wide genetic framework to identify mechanisms of social effects

Phenotypes are shaped not only by an individuals genotype (direct genetic effects, DGE) and environment but also by the genetic composition of social partners through indirect genetic effects (IGE). Although IGE have been detected across many traits and species, their mechanisms remain largely unknown, particularly for physiological traits. Here we introduce a phenome-wide genetic framework that identifies proxy phenotypes for the heritable traits of social partners mediating IGE by estimating genetic correlations between IGE on focal phenotypes and DGE on measured traits. Applying this approach to two large, outbred mouse datasets comprising hundreds of behavioural and physiological phenotypes, we find that behavioural traits are neither more affected by IGE nor better proxies for the traits mediating them, challenging the prevailing behavioural-centric view of social effects. Instead, immune, metabolic and growth phenotypes are both affected by IGE and informative proxies for their underlying mechanisms, potentially reflecting the social transmission of gut microbes. Our framework provides a novel strategy to better understand the genetic basis of complex traits and uncover mechanisms of social effects.

genetics↗

bioRxiv2025

Genomic and phenotypic characterization of novel jumbo and small bacteriophages infecting Xanthomonas hortorum pv. vitians: Toward a phage-based biocontrol strategy

In recent years, the use of bacteriophages as biocontrol agents has gained renewed attention, especially for targeting major phytopathogenic genera like Xanthomonas. However, their potential against Xanthomonas hortorum pv. vitians, the causal agent of bacterial leaf spot of lettuce, remains largely unexplored with only two lytic phages reported to date. In this study, eight novel lytic tailed phages were isolated from wastewater samples, including three jumbophages, which are the first known to infect this pathovar. These jumbophages define a new viral genus and exhibit distinct biological characteristics, including broader host ranges, but lower burst sizes and slower lytic cycles compared to the smaller-genome phages. Together, the newly isolated phages exhibited lytic activity against nearly all X. hortorum pv. vitians strains tested while remaining highly specific to the pathovar. Genomic analyses revealed strictly lytic profiles, and absence of virulence or resistance genes, supporting their biosafety for agricultural use. Furthermore, the isolation of a phage infecting a bacterial mutant previously shown to be resistant to the virulent phage {Phi}Xhv-1 highlights the potential for designing robust phage cocktails to mitigate resistance emergence. All phages demonstrated high stability across a wide range of pH and temperature conditions, but remained highly sensitive to UV exposure. These findings provide a valuable foundation for developing phage-based biocontrol strategies against bacterial leaf spot of lettuce. IMPORTANCERanked among the leading plant-pathogenic bacterial genera, Xanthomonas species affect a wide range of crops and contribute to major agricultural losses worldwide. Among these, Xanthomonas hortorum pv. vitians, the causal agent of bacterial leaf spot of lettuce, poses a serious threat to lettuce production worldwide. Currently, no effective disease managements strategies are available to reduce this foliar hemibiotropic phytopathogen. Bacteriophage-based biocontrol has shown promising results against Xanthomonas spp. However, its application against this pathogen remains largely unexplored, with only two phages isolated to date. Successful phage application in agriculture requires careful selection and through characterization to ensure safety and efficacy. In this study, the phage diversity targeting this phytopathogen was expanded through the isolation of eight novel lytic phages, including the first jumbophages infecting this species. Their genomic and biological properties provide a valuable foundation for developing future phage-based treatment against this challenging pathogen.

microbiology↗

bioRxiv2025

Novel insights into the genetic architecture and mechanisms of host/microbiome interactions from a multi-cohort analysis of outbred laboratory rats

The intestinal microbiome influences health and disease. Its composition is affected by host genetics and environmental exposures. Understanding host genetic effects is critical but challenging in humans, due to the difficulty of detecting, mapping and interpreting them. To address this, we analysed host genetic effects in four cohorts of outbred laboratory rats exposed to distinct but controlled environments. We found that polygenic host genetic effects were consistent across environments. We identified three replicated microbiome-associated loci, one of which involved a sialyltransferase gene and Paraprevotella. We found a similar association in a human cohort, between ST6GAL1 and Paraprevotella, both of which have been linked with immune and infectious diseases. Moreover, we found evidence of indirect genetic effects on microbiome phenotypes, which substantially increased their total genetic variance. Finally, we identified a novel mechanism whereby indirect genetic effects can contribute to "missing heritability".

genetics↗

bioRxiv2024

Draft genome of Palmaria palmata and intraspecific genetic variations in the North-East Atlantic

The rhodophyte Palmaria palmata (L.) Weber & Mohr is one of the target species of a growing European seaweed industry due to its high content of protein and essential amino acids which makes it suitable for human food, dietary supplements, and as salmon feed. However, the lack of a published nuclear genome limits phylogenetics analyses and gene function investigations which could help the development of a breeding programme. We present the first draft genome of P. palmata that was obtained with PacBio HiFi long read sequencing with average coverage of 10x, consisting of an assembly of 1.05 Gb, N50=2.75Mb and BUSCO completeness of 72.1%. Additionally, a population study on the whole genome of 33 P. palmata individuals from across the Northern East Atlantic area found three main clusters consistent with their geographic distribution: (1) Denmark and Norway, (2) France and western Ireland, (3) Faroe Islands. All individuals from Northern Ireland share ancestry with western Ireland and Denmark, and some individuals from the Faroe Islands show admixture from Faroe, western Ireland and Northern Ireland. These results represent a fundamental step towards breeding and genetic studies to further explore the vastly unexploited economic potential of Palmaria palmata. Highlights- We report the first draft genome of Palmaria palmata, from PacBio HiFi long reads. - The size of the genome, 1.05 Gb, is among the largest so far among the Rhodophyta. - Busco completeness of 72.1% and contig N50 of 2.75 Mb indicate good quality. - The genomes of 33 more individuals from North Atlantic Europe have been sequenced. - Phylogenetic analysis found three clusters consistent with geographic distribution.

genomics↗

bioRxiv2024

Ribosomal composition affects the noncanonical translation and toxicity of polyglycine-containing proteins in fragile X-associated conditions

Expansion of CGG repeats (CGGexp) in the 5 untranslated region (5UTR) of the FMR1 gene underlies the fragile X premutation-associated conditions including tremor/ataxia syndrome, a late-onset neurodegenerative disease and fragile X-associated primary ovarian insufficiency. One common pathomechanism of these conditions is the repeat-associated non-AUG-initiated (RAN) translation of CGG repeats of mutant FMR1 mRNA, resulting in production of FMRpolyG, a toxic protein containing long polyglycine tract. To identify novel modifiers of RAN translation we used an RNA-tagging system and mass spectrometry-based screening. It revealed proteins enriched on CGGexp-containing FMR1 RNA in cellulo, including a ribosomal protein RPS26, a component of the 40S subunit. We demonstrated that depletion of RPS26 and its chaperone TSR2, modulates FMRpolyG production and its toxicity. We also found that the RPS26 insufficiency impacted translation of limited number of proteins, and 5UTRs of mRNAs encoding these proteins were short and guanosine and cytosine-rich. Moreover, the silencing of another component of the 40S subunit, the ribosomal protein RPS25, also induced repression of FMRpolyG biosynthesis. Results of this study suggest that the two 40S ribosomal proteins and chaperone TSR2 play an important role in noncanonical CGGexp-related RAN translation.

molecular biology↗

bioRxiv2023

Targeted Metagenomic Databases Provide Improved Analysis of Microbiota Samples

We introduce Moonbase, a flexible pipeline that can be used to build targeted, project-specific, databases in order to improve the accuracy of taxonomic detection and quantification in complex microbial communities. Moonbase was evaluated using synthetic metagenomic samples and compared against existing methods including MetaPhlAn3 and generalized Kraken2 databases. Our results indicate that Moonbase significantly improves species precision and quantification, outperforming marker genes and generalized databases. Construction of a phylogenetic tree from 16S data of genomes in Moonbase allows for the incorporation of UniFrac-type phylogenetic information into diversity calculations of samples. We demonstrate the resulting analysis has increased statistical power in distinguishing microbial communities. This study highlights the continual evolution of metagenomic tools with the goal of improving metagenomic analysis and highlights the potential of the Moonbase pipeline.

bioinformatics↗

bioRxiv2023

Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing

BackgroundDominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena played a major role in quantitative genetics. However, today most genome-wide association studies (GWAS) assume alleles act additively. MethodsWe systematically investigated both dominance - here representing any non-additive effect - and additivity across 574 physiological and gene expression traits in three mammalian models: a Pig F2 Intercross, a Rat Heterogeneous Stock and a Mouse Heterogeneous Stock. ResultsIn all species, and across all physiological traits, dominance accounts for about one quarter of the heritable variance. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable assuming additivity, we identified 154, 64 and 62 novel dominance QTLs in pigs, rats and mice respectively, that were undetectable as additive QTLs. Similarly, even though most cis-acting eQTLs are additive, we observed a large fraction of dominance variance in gene expression, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, in HS rat transcriptomes, thousands of eQTLs associate with alternate transcripts and exhibit complex additive and dominant architectures, suggesting a mechanism for dominance. ConclusionsAlthough heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality.

genetics↗

bioRxiv2019

Traces of past transposable element presence in Brassicaceae genome dark matter

AO_SCPLOWBSTRACTC_SCPLOWTransposable elements (TEs) are mobile, repetitive DNA sequences that make the largest contribution to genome bulk. They thus contribute to the so-called "dark matter of the genome", the part of the genome in which nothing is immediately recognizable as biologically functional. We developed a new method, based on k-mers, to identify degenerate TE sequences. With this new algorithm, we detect up to 10% of the A. thaliana genome as derived from as yet unidentified TEs, bringing the proportion of the genome known to be derived from TEs up to 50%. A significant proportion of these sequences overlapped conserved non-coding sequences identified in crucifers and rosids, and transcription factor binding sites. They are overrepresented in some gene regulation networks, such as the flowering gene network, suggesting a functional role for these sequences that have been conserved for more than 100 million years, since the spread of flowering plants in the Cretaceous.

genomics↗

bioRxiv2018

Genome-wide association study of social genetic effects on 170 phenotypes in laboratory mice

The phenotype of one individual can be affected not only by the individuals own genotypes (direct genetic effects, DGE) but also by genotypes of interacting partners (indirect genetic effects, IGE). IGE have been detected using polygenic models in multiple species, including laboratory mice and humans. However, the underlying mechanisms remain largely unknown. Genome-wide association studies of IGE (igeGWAS) can point to IGE genes, but have not yet been applied to non-familial IGE arising from "peers" and affecting biomedical phenotypes. In addition, the extent to which igeGWAS will identify loci not identified by dgeGWAS remains an open question. Finally, findings from igeGWAS have not been confirmed by experimental manipulation. We leveraged a dataset of 170 behavioural, physiological and morphological phenotypes measured in 1,812 genetically heterogeneous laboratory mice to study IGE arising between same-sex, adult, unrelated laboratory mice housed in the same cage. We developed methods for igeGWAS in this context and identified 24 significant IGE loci for 17 phenotypes (FDR < 10%). There was no overlap between IGE loci and DGE loci for the same phenotype, which was consistent with the moderate genetic correlations between DGE and IGE for the same phenotype estimated using polygenic models. Finally, we fine-mapped seven significant IGE loci to individual genes and confirmed, in an experiment with a knockout model, that Epha4 gives rise to IGE on stress-coping strategy and wound healing. Our results demonstrate the potential for igeGWAS to identify IGE genes and shed some light into the mechanisms of peer influence.

genetics↗

bioRxiv2018

A High-Resolution Genetic Map for the Laboratory Rat

An accurate and high-resolution genetic map is critical for mapping complex traits, yet the resolution of the current rat genetic map is far lower than human and mouse, and has not been updated since the original ensen-Seaman map in 2004. For the first time, we have refined the rat genetic map to sub-centimorgan (cM) r solution (<0.02 cM) by using 95,769 genetic markers and 870 informative meioses from a cohort of 528 heterogeneous stock (HS) rats. Global recombination rates in the revised sex-averaged map (0.66 cM/Mb) did not difeer compared to the historical map (0.65 cM/Mb); however, substantial refinement was made to the localization of highly recombinant regions within the revised map. Also for the first time, sex-specific rat genetic maps were generated, which revealed both genomewide and fine-scale variation in recombination rates between male and female rats. Reanalysis of multiple quantitative trait loci (QTL) using the historical and refined rat genetic maps demonstrated marked changes to QTL localization, shape, and effect size. As a resource to the rat research community, we have provided revised centimorgan positions for all physical positions within the rat genome and commonly used genetic markers for trait mapping, including 44,828 SSLP markers and the RATDIV genotyping array. Collectively, this study provides a substantial improvement to the rat genetic map and an unprecedented resource for analysis of complex traits and recombination in the rat.

genetics↗