Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Synthesis and characterization of a catalyst containing vanadium supported on alumina

This work describes the preparation, the characterization of the hysico chemical properties of catalyst containing vanadium supported on Al$_{2}$O$_{3}$, and study of its catalytic activity in the reaction of conversion of SO$_{2}$ to SO$_{3}$, the synthesis of the alumine was carried out by hydrolysis of isopropoxyde aluminium in solution of isopropanol. Vanadium is introduced by impregnation with porous volume in several stages. The same technique is used for the SO$_{4}{}^{2-}$, K$_{2}$O.followed of calcination under-air with 450$^{\circ}$C. This solid is characterized by DRX, IR and analyzes elementary. IR highlighted the presence of the surface sulphated species, adsorption of the molecule probes 2,6-dimethylpyridine on V$_{2}$O$_{5}$/Al$_{2}$O$_{3}$ followed by infra-red shows the presence of coordinated species (Lewis acidity) about 1580, 1470 and 1452 cm$^{-1}$and protonic species (Brönsted acidity) characterized by vibrations infra-red about 1650 and 1620 cm$^{-1}$

Phenotypic diversity analysis of mandarin varieties from the Moroccan collection of Kenitra INRA

Parmi les agrumes, les mandarines sont caractérisées par une grande diversité d'espèces, mais seules quelques variétés sont commercialisées. L’objectif de cette étude vise à caractériser et évaluer 70 variétés du mandarinier à partir du germoplasme des agrumes à l’INRA de Kenitra selon les critères morphologiques et physico-chimiques sur quatre années consécutives. Des différences hautement significatives ont été révélées pour tous les caractères étudiés. De même, le coefficient de maturité a permis de classer les variétés en trois groupes (Tardives, précoces et demi saison). Ces groupes offrent une grande possibilité de choix de parents pour la création de variétés améliorées de mandarinier à fruits sans pépins et ayant un potentiel de rendement élevé. De plus, l’analyse de cluster basée sur des données qualitatives et quantitatives a classé toutes les variétés en trois grands groupes dont chacun contient des variétés phénotypiquement proches. Le germoplasme de mandariniers pourrait soutenir un programme de création variétale et bénéficier d’une nouvelle stratégie de conservation ex situ.Among the Citrus genus, mandarins are characterized by a large diversity of species, but only a few varieties are marketed. The objective of this study is to characterize and evaluate 70 varieties of mandarins from the Citrus germplasm at INRA Kenitra according to morphological and physico-chemical criteria over four consecutive years. Highly significant differences were revealed for all the traits studied. Like Wase, the maturity coefficient made it possible to classify the varieties in three groups (Late, early and half season). These groups offer a large possibility of choice of parents for the creation of seedless mandarins with high yield potential. In addition, the cluster analysis based on qualitative and quantitative data classified all varieties into three large groups, each of which contains phenotypic close varieties. The mandarin germplasm could underlie a varietal creation program and a new strategy of preservation ex sit

Analyse de la diversité phénotypique des variétés de mandariniers issues de la collection marocaine INRA Kenitra

Among the Citrus genus, mandarins are characterized by a large diversity of species, but only a few varieties are marketed. The objective of this study is to characterize and evaluate 70 varieties of mandarins from the Citrus germplasm at INRA Kenitra according to morphological and physico-chemical criteria over four consecutive years. Highly significant differences were revealed for all the traits studied. Like Wase, the maturity coefficient made it possible to classify the varieties in three groups (Late, early and half season). These groups offer a large possibility of choice of parents for the creation of seedless mandarins with high yield potential. In addition, the cluster analysis based on qualitative and quantitative data classified all varieties into three large groups, each of which contains phenotypic close varieties. The mandarin germplasm could underlie a varietal creation program and a new strategy of preservation ex situParmi les agrumes, les mandarines sont caractérisées par une grande diversité d'espèces, mais seules quelques variétés sont commercialisées. L’objectif de cette étude vise à caractériser et évaluer 70 variétés du mandarinier à partir du germoplasme des agrumes à l’INRA de Kenitra selon les critères morphologiques et physico-chimiques sur quatre années consécutives. Des différences hautement significatives ont été révélées pour tous les caractères étudiés. De même, le coefficient de maturité a permis de classer les variétés en trois groupes (Tardives, précoces et demi saison). Ces groupes offrent une grande possibilité de choix de parents pour la création de variétés améliorées de mandarinier à fruits sans pépins et ayant un potentiel de rendement élevé. De plus, l’analyse de cluster basée sur des données qualitatives et quantitatives a classé toutes les variétés en trois grands groupes dont chacun contient des variétés phénotypiquement proches. Le germoplasme de mandariniers pourrait soutenir un programme de création variétale et bénéficier d’une nouvelle stratégie de conservation ex situ

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old