Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Use Of Anatomical, Chemical, And Molecular Genetic Characteristics In The Quality Control Of Medicinal Species: A Case Study Of Sarsaparilla (smilax Spp.)

Use of Anatomical, Chemical, and Molecular Genetic Characteristics in the Quality Control of Medicinal Species: A Case Study of Sarsaparilla (Smilax spp.) Species of the genus Smilax, popularly known as sarsaparilla, are used in folk medicine as a tonic, an anti-rheumatic, and an anti-syphilis treatment, and are sold in Brazilian drugstores without any quality control regarding their origin and efficacy. The origin of the material is mainly based on wild extraction. Quality control of herbal drugs should include a more reliable identification of the source involving characterization and definition of their anatomical and chemical characteristics. The current study aimed to verify whether the combined use of anatomical, chemical, and molecular genetic characteristics might be useful in the quality control of medicinal plants, specifically the sarsaparilla sold in compounding drugstores in the state of São Paulo, Brazil. Root samples were subjected to conventional light microscopy and scanning electron microscopy. To determine the chemical profile, thin-layer chromatography (TLC) was applied to ethanol extracts of the roots. The chemical profile of the chemical material sold in stores was compared with the previously determined profiles of medicinal Smilax species (S. goyazana, S. rufescens, S. brasiliensis, S. campestris, S. cissoides, S. fluminensis, S. oblongifolia, and S. polyantha). Although there was considerable similarity between the anatomical structure of the commercial sarsaparilla and the structure reported in the literature for the Smilax species, there were differences in the phloem organization and in the presence of a series of idioblasts containing raphides, phenolic idioblasts, and metaxylem in the center of the plant structure. TLC analysis of the commercial ethanol extracts revealed spots with colors ranging from yellow to green. In addition, the same spots showed components with the same retention factor (Rf), indicating chemical similarity between the different samples. However, the distribution pattern of the spots, as well as the Rf of the commercial samples, differed from those obtained for the eight species of Smilax, which were very similar to each other. Comparing the groups examined in the present study with regard to microsatellite markers and DNA barcoding revealed that commercial sarsaparilla is genetically different from the eight species of Smilax known for their medicinal properties in Brazilian ethnobotanical surveys. This seriously calls into question their effectiveness. This case study of sarsaparilla demonstrates the utility of anatomical, chemical, and molecular genetic characteristics in the quality control of medicinal plants.684410425Alves, P.F., Caracterização genética de populações de Caryocar brasiliense Camb. e Jatropha curcas L., espécies potenciais para o biodiesel. 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