HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Does Methyl-CpG-binding domain protein 2 (MBD2) repress gene transcription?: A meta-analysis of transcriptome studies after MBD2 perturbation
No full textInternational audienceContext: Methyl-CpG-binding domain protein 2 (MBD2) binds methylated CpG in vitro or in vivo, and recruit the NuRD repressive complex. MBD2 is thought to play a role in the transcriptional repression of genes with a methylated promoter in vertebrates. However in surprising study, a quadruple knock-out of MBD2 along with MECP2, MBD1, and MBD4 lead to no widespread up-regulation of genes with a methylated promoters.Methods: A meta-analysis of transcriptome studies after MBD2 perturbation was carried out to investigate the contradictory results observed in the literature. Twenty-seven datasets were identified from 17 different studies in human or mouse, including 26 datasets with MBD2 removal and one dataset with MBD2 over-expression. The number of up-regulated or down-regulated genes was identified for each study using a differentially expressed gene reanalysis with {limma}, using four different null-hypothesis thresholds of fold-change. MBD2 perturbation was confirmed for 19 of the 26 datasets.Results: Eleven of the 18 datasets (61%) with MBD2 removal were showing more gene over-expressions than down-regulations, while the other datasets were showing more down-regulations than over-expressions (4 datasets), or balanced profiles (3 datasets). The number of up-regulated genes after MBD2 removal was globally estimated as 3.2 times (CI 95%: 1.4; 7.3) more than the number of down-regulated genes for a fold change threshold of 2. The only datasets with MBD2 over-expression had more down-regulated genes than upregulated genes. There was no obvious association between the role of MBD2 as a gene repressor and the species, the tissues / cell types, its oncogenic status, nor the perturbation method.Conclusion: This meta-analysis supports a role for MBD2 in gene repression
Thermoneutral housing worsens MASLD and reveals defective brown adipose tissue response to β3-adrenergic stimulation
No full textInternational audienceMetabolic dysfunction-associated steatotic liver disease (MASLD), and its more advanced stage metabolic dysfunction-associated steatohepatitis, is the most common chronic liver disease, constituting a major public health issue. Relevant preclinical models are needed to define molecular mechanisms underlying MASLD pathogenesis and evaluate therapeutic approaches. The majority of the lipids accumulating in the liver upon MASLD originate from adipose tissue and appropriate models to study the liver-adipose tissue dialog are also needed. Here, we demonstrated that, compared to standard temperature housing, thermoneutral housing aggravated western diet (WD)-induced obesity, diabetes, and steatosis in male mice, which was associated with increased hepatic expression of inflammation- and fibrosis-related genes. Accordingly, thermoneutral-housed WD-fed mice developed more severe hepatic inflammation and fibrosis compared to standard-housed mice. We next used thermoneutral-housed WD-fed mice to question the effect of MASLD during β3-adrenergic stimulation. We found that diet-induced MASLD is associated with defective inter-organ metabolic cross-talk which leads to impaired activation of brown adipose tissue
Gain and loss of gene function shaped the nickel hyperaccumulation trait in Noccaea caerulescens
No full textInternational audienceNickel hyperaccumulation is an extreme adaptation to ultramafic soils observed in more than 500 plant species. However, our understanding of the molecular mechanisms underlying the evolution of this trait remains limited. To shed light on these mechanisms, we have generated a high-quality genome assembly of the metal hyperaccumulator Noccaea caerulescens. We then used this genome as reference to conduct comparative intraspecific and interspecific transcriptomic analyses using various accessions of N. caerulescens and the non-accumulating relative Microthlaspi perfoliatum, to identify genes associated with nickel hyperaccumulation. Our results suggest a correlation between nickel hyperaccumulation and a decrease in the expression of genes involved in defense responses and the regulation of membrane trafficking. Surprisingly, these analyses did not reveal a significant enrichment of genes involved in the regulation of metal homeostasis. However, we found that the expression levels of selected metal transporters, namely NcHMA3, NcHMA4 and NcIREG2, is consistently elevated in N. caerulescens accessions hyperaccumulating nickel. Furthermore, our analyses identified frameshift mutations in NcIRT1 associated with the loss of nickel hyperaccumulation in a few accessions. We further showed that the expression of a functional NcIRT1 in roots of the La Calamine accession increases nickel accumulation in shoots. Our results demonstrate that NcIRT1 participate in nickel hyperaccumulation in N. caerulescens. They also suggest that nickel hyperaccumulation is an ancient trait in N. caerulescens that has evolved from the high and constitutive expression of few metal transporters including NcIREG2 and that the trait was subsequently lost in a few accessions due to mutations in NcIRT1
Promising Effects of Duck Vaccination against Highly Pathogenic Avian Influenza, France 2023–2024
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Séroprévalence de la néosporose chez le chien dans l'agglomération toulousaine
No full textNeospora caninum is a protozoan that affects cattle, causing abortions, and dogs, where infection is generally asymptomatic. Few data are available in France on the seroprevalence of this parasite in the canine population. Our work is part of a research project funded by the Société Française Canine-Agria. Our study complements work carried out at the CHUVAC d'Alfort. 508 sera from dogs consulting the ENVT's CHUVAC between January 2020 and February 2023 were analyzed by a competitive ELISA kit. The estimated seroprevalence in this medicalized dog population was 5.7%. A significantly higher seroprevalence was observed in purebred dogs (13.2%). The other factors studied were not statistically significant. This rate is comparable to other European studies. The search for this parasite should be considered more systematically in the case of neurological disorders in dogs.Neospora caninum est un protozoaire affectant les bovins et provoquant des avortements, et les chiens où l’infection est généralement asymptomatique. Peu de données sont disponibles en France concernant la séroprévalence de ce parasite dans la population canine. Notre travail s’inscrit dans un projet de recherche financé par la Société Française Canine-Agria. Notre étude complète le travail effectué au CHUVAC d’Alfort. 508 sérums de chiens consultant le CHUVAC de l’ENVT entre janvier 2020 et février 2023 ont été analysés par un kit ELISA en compétition. La séroprévalence estimée au sein de cette population canine médicalisée a été de 5,7%. Une séroprévalence significativement plus importante a été observée chez les chiens de pure race (13.2%). Les autres facteurs étudiés n’ont pas été statistiquement significatifs. Ce taux est comparable aux autres études européennes. La recherche de ce parasite devrait être envisagée plus systématiquement lors de troubles neurologiques chez le chien
Further characterization of the structural variant upstream of the KIT gene underlying head depigmentation across a diverse panel of cattle breeds
No full textInternational audienceA previous study based on a taurine pangenome uncovered a structural variant upstream of the KIT gene associated with depigmentation in white-headed cattle. In this study, we aimed to deepen our understanding of this region by analysing a collection of 80 genome assemblies from 20 different cattle breeds, including several not previously investigated. Using a combination of complementary approaches, we constructed a 2 Mb pangenome graph encompassing the KIT gene and the depigmentation-associated region to investigate the spectrum of structural variations within this region. Our analysis revealed a more fragmented structure than previously reported, mainly due to the inclusion of a larger number of assemblies (80 vs. 24) with varying sequencing technologies’ quality (CLR and HiFi). Despite this increased complexity, the identified structural variant’s alleles closely mirrored those reported in earlier study and depicting clear segregation of the population into two distinct groups. The first group includes breeds characterized by a white-headed phenotype and the second group contains all non-white headed breeds. We further validated this structural variant by aligning short-reads to the pangenome graph and genotyping several hundred animals for this structural variant. Our results provide new insights into the genetic mechanisms underlying head depigmentation in cattle and demonstrate the power of pangenome-based analyses for detecting trait-associated structural variations. This research was supported by funding from the Agreenium programme, with contributions from the Biosphera Graduate School, the ABIES doctoral school, the INRAE Animal Genetics division, and the INRAE GBOS team from the GABI department
Worldwide analysis of the variability of microRNA genes in domestic goats
No full textInternational audienceMicroRNAs (miRNAs) are a type of small non-coding RNAs involved in the post-transcriptional repression of target mRNA transcripts, and responsible for the fine-tuning of numerous molecular mechanisms regulating cell metabolism. The presence of single nucleotide polymorphisms (SNP) in miRNA genes is known to affect their expression dynamics and binding affinity towards targeted mRNAs, thus potentially modifying gene regulatory networks. Since domestication, goats have spread worldwide, adapting to diverse environmental conditions. However, a comprehensive analysis of how evolutionary forces across and within continental regions have influenced the genome-wide distribution of miRNA polymorphisms in domestic goats is still lacking. By using whole-genome sequencing data from 1,059 domestic goats with African, Asian, American and European origins, we have identified SNPs located within and around goat miRNA genes. In doing so, we have found that miRNA SNPs display very low alternative allele frequencies (median alternative allele frequency of 0.38%) and that the distribution of SNPs within and around miRNA genes is uneven. Remarkably, the stem, loop and neighboring regulatory regions of precursor miRNA hairpins show a significantly higher SNP density compared to the miRNA seed, which determines the binding affinity to target mRNAs. This outcome is probably explained by the occurrence of strong purifying selection removing polymorphisms with potential effects on gene regulatory networks linked to miRNA function. Moreover, we have detected a differential segregation of miRNA SNPs across and within continental regions, with an enriched segregation of putatively high-impact polymorphisms—those located in the seed and other biologically relevant regions of miRNA genes—in isolated goat populations with a low census and reduced heterozygosity. Such information could be useful to investigate the phenotypic consequences of miRNA polymorphisms disrupting gene regulatory networks in domestic goats, as well as to assess their potential impact on adaptation and fitness
A Strategy for Balanced Haplotype-Resolved De Novo Assembly of the Autotetraploid Genome of Medicago sativa
No full textInternational audienceWe present novel French Medicago sativa haplotyped genome assemblies. They have been optained using high quality long reads as well as Hi-C short reads. Haplotypes have been separated using constraint programming
Invited review: Mastitis Escherichia coli strains—Mastitis-associated or mammo-pathogenic?
No full textInternational audienceBovine mastitis remains a major concern for dairy farmers, mainly because of its effect on the economy of their activity and on animal welfare. Because Escherichia coli is considered a major mastitis pathogen, the diversity of E. coli strains isolated from mastitis cases has been studied for decades, with the aim to discover new ways to fight this infection. With the recent advances in whole-genome sequencing, a detailed view of the peculiarities of mastitis E. coli strains has emerged. This review aims to bring together the knowledge garnered over the years with the more recent results of whole-genome analyses. Whereas the concept of a mammary pathogenic E. coli has been proposed, because a common set of virulence genes cannot be identified among mastitis E. coli strains, we prefer the use of mastitis-associated E. coli (MAEC), with MAEC being more an "ecotype" rather than a "pathotype." Indeed, data available so far suggest that a common feature of MAEC would rather be an enrichment in fitness capabilities that makes them well-suited for survival and rapid adaptation to changing biotopes in the mammary gland, which we qualify as intramammary ecotopes
Climate resilience differs across dairy sheep populations in Europe
No full textInternational audienceThe dairy sheep sector in Europe is characterised by the wide range of breeds involved, the variety of environments and the existence of well-established selection schemes. The goal of this study was to characterise the productive response to changes in thermal load (TL) across dairy sheep breeds in Europe, both at the population and the individual levels. Milk, fat and protein test day yields data from five dairy breeds, Assaf (As), Chios (Ch), Lacaune (Lc), Latxa (Lt) and Manchega (Mn) were used. Overall, 682 972 ewes from 827 flocks participated in the study. The breeds differed in the climatic region of origin and breeding area, varying from temperate (Lc and Lt) to warm (As, Ch, Mn), and, in the intensity of the selection programmes, with As and Lc more intensely selected. Historical production data were combined with meteorological information at the date of recording. Reaction norm models with polynomial functions in mixed model settings were fitted. Substantial variability in the population response to changes in TL was observed across breeds. Mn and Ch, with similar levels of production and climatic conditions, displayed greater sensitivity to cold than to hot conditions. On the other hand, the Lt breed showed the highest tolerance to cold stress and was moderately sensitive to heat. The most productive breeds, As and Lc, showed the largest sensitivity to cold (CS) or heat (HS) stress, with As/Lc showing the greatest production loss associated with cold/heat stress. Individual variability in response to thermal stress was observed in all breeds for the two extremes. However, variability in slopes of response was substantially lower than the overall variability of the trait, ranging from 4%/degrees C for all traits under CS to 17%/degrees C for fat yield under HS, in the Lc breed. For all breeds, a negative correlation was estimated between the individual level of the traits and heat tolerance, indicating antagonism between high production and heat tolerance. However, this antagonism was mild in Mn (-0.19 or milk yield and-0.28 for fat and protein yield) and largest for Lc (-0.77, -0.96 and-0.70 for milk, fat and protein yields, respectively). Given the expected increase in temperatures associated with climate change, dairy sheep farming based on the breeds less adapted with warm conditions and also for the more intensive systems based on highly producing animals will need to implement heat abatement strategies or incorporate heat tolerance in the selection programmes to improve future adaptation. (c) 2025 The Authors. Published by Elsevier B.V. on behalf of The animal Consortium