Dissection génétique des caractères par analyse de liaison et d'association (aspects méthodologiques et application à la sensibilité à l'ostéochondrose chez les Trotteurs Français)

Diverses lésions ostéochondrales peuvent affecter les articulations des jeunes chevaux et réduire leurs futures performances en course. L objectif de cette thèse est d identifier les régions du génome, appelées locus à caractère quantitatif (QTL), associées avec des caractères mesurant l ostéochondrose (OC) enregistrés dans le programme GENEQUIN sur une population de Trotteurs Français. Le génotypage a été réalisé à l aide de la puce SNP Illumina BeadChip EquineSNP50, qui est dense et permet d exploiter le déséquilibre de liaison par des analyses d association. Ces analyses sont sujettes à certains problèmes en présence d une structure familiale des données. Dans la première partie de la thèse, une comparaison de la puissance et de la robustesse d un choix restreint de méthodes d analyses est effectuée. L originalité de ce travail réside dans la dérivation algébrique des moments des distributions des statistiques de test comparées, donnant ainsi plus de généralité à nos résultats et permettant une meilleure compréhension des différences. Les résultats peuvent notamment servir à l optimisation du dispositif expérimental. La deuxième partie est consacrée à la cartographie des régions QTL des caractères mesurant l OC en différents sites articulaires dans une population de 583 Trotteurs Français. Cette étude a permis de mettre en évidence plusieurs régions QTL d effets moyens et faibles à un niveau significatif mais pas hautement significatif. Nous montrons que l OC est un caractère polygénique et qu aucun QTL, ayant un effet à la fois sur l OC du jarret et l OC du boulet, n est détectable dans ce protocole QTL, ce qui infirme l hypothèse simple d une cause génétique commune de la sensibilité à cette maladie sur les différents sites anatomiques. Suite à ces travaux, l identification des gènes candidats et des mutations causales devrait clarifier la physiopathologie moléculaire de l OC et ainsi permettre de développer des stratégies efficaces pour l évaluation des risques. Pendant ce temps, les marqueurs peuvent être utilisés dans un contexte de sélection assistée par marqueurs afin d améliorer la santé et le bien-être du cheval.Osteochondral lesions are commonly observed in young horses and may be responsible for reduced performances in racing. The purpose of the PhD thesis was to identify genome regions, called quantitative trait loci (QTL), associated with various traits measuring osteochondrosis (OC) and recorded in the GENEQUIN program in a population of French Trotters horses. Genotyping was performed using the EquineSNP50 Illumina high density chip, which allows to exploit the linkage disequilibrium with genome-wide association studies. These analyses are subject to several problems in presence of family structure. We hence first proposed a comparison of power and robustness of a limited choice of models for this type of analysis. The originality of this work lies in the algebraic derivation of the distribution moments of the test statistics compared, making the outcome of this comparison more general and allowing a better understanding of differences. The results can be used to establish an experimental design. The second part was devoted to the QTL fine mapping of traits that measure OC in different joint sites. This study highlighted several significant QTL with low and medium effects but none of them were highly significant. We showed that OC is a polygenic trait and we were not able to identify QTL affecting both OC on the hock and the fetlock, rejecting the hypothesis of a single genetic determinism of susceptibility to this desease accross anatomical sites. Further studies will now focus on the identification of candidate genes and screening for mutation in an attempt to clarify the molecular physiopathology of OC and develop efficient strategies for risk assessment. Meanwhile, markers could be used in a marker-assisted selection context to improve horse health and welfare.TOULOUSE-ENSAT-Documentation (315552324) / SudocSudocFranceF

Co-Design Of Agroecological Temperate Fruit Tree Systems: Approach, Tradeoffs And Outputs

Crop diversification and ecological intensification are a way to foster ecosystem services and produce in very low input systems. We analyzed the design process of three experimental sites that shared the same objective of ecological intensification and diversification in fruit tree production. Agronomic, ecological and organizational aspects were involved in the approach. Pest suppressive plant diversification, resource sharing among cultivated and associated plants, and feasibility were key elements. Identifying the expected functions of each plant species or assemblage (e.g. barrier, trap, production) was also crucial. Co-design brought experiences and expertises and was a powerful way to obtain trade-offs between targeted services in the design of innovative fruit production systems being now experimented. Further research and evaluation of the experimented prototypes are still required but the present analysis opens avenues for agroecological design in perennial crops

Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

Background: Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment. Methods: A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months. Results: The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out. Conclusions: Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Detection of a Cis eQTL Controlling BMCO1 Gene Expression Leads to the Identification of a QTG for Chicken Breast Meat Color

Classical quantitative trait loci (QTL) analysis and gene expression QTL (eQTL) were combined to identify the causal gene (or QTG) underlying a highly significant QTL controlling the variation of breast meat color in a F2 cross between divergent high-growth (HG) and low-growth (LG) chicken lines. Within this meat quality QTL, BCMO1 (Accession number GenBank: AJ271386), encoding the β-carotene 15, 15′-monooxygenase, a key enzyme in the conversion of β-carotene into colorless retinal, was a good functional candidate. Analysis of the abundance of BCMO1 mRNA in breast muscle of the HG x LG F2 population allowed for the identification of a strong cis eQTL. Moreover, reevaluation of the color QTL taking BCMO1 mRNA levels as a covariate indicated that BCMO1 mRNA levels entirely explained the variations in meat color. Two fully-linked single nucleotide polymorphisms (SNP) located within the proximal promoter of BCMO1 gene were identified. Haplotype substitution resulted in a marked difference in BCMO1 promoter activity in vitro. The association study in the F2 population revealed a three-fold difference in BCMO1 expression leading to a difference of 1 standard deviation in yellow color between the homozygous birds at this haplotype. This difference in meat yellow color was fully consistent with the difference in carotenoid content (i.e. lutein and zeaxanthin) evidenced between the two alternative haplotypes. A significant association between the haplotype, the level of BCMO1 expression and the yellow color of the meat was also recovered in an unrelated commercial broiler population. The mutation could be of economic importance for poultry production by making possible a gene-assisted selection for color, a determining aspect of meat quality. Moreover, this natural genetic diversity constitutes a new model for the study of β-carotene metabolism which may act upon diverse biological processes as precursor of the vitamin A

2021 DORIS definition of remission in SLE: final recommendations from an international task force.

OBJECTIVE: To achieve consensus on a definition of remission in SLE (DORIS). BACKGROUND: Remission is the stated goal for both patient and caregiver, but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a framework for such a definition, without reaching a final recommendation. METHODS: Several systematic literature reviews were performed and specific research questions examined in suitably chosen data sets. The findings were discussed, reformulated as recommendations and voted on. RESULTS: Based on data from the literature and several SLE-specific data sets, a set of recommendations was endorsed. Ultimately, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical systemic lupus erythematosus disease activitiy index (SLEDAI)=0, Evaluator's Global Assessment <0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials, immunosuppressives, and biologics. CONCLUSION: The 2021 DORIS definition of remission in SLE is recommended for use in clinical care, education, and research including clinical trials and observational studies