The relationships among rock groups between the Grand Lake Thrust and Cabot Fault, west Newfoundland

The area between the Grand Lake Thrust and the Cabot Fault is underlain by metamorphic rocks that separate the most easterly exposures of the west Newfoundland carbonate terrane from the most westerly exposures of ophiolitic and volcanic rocks of central Newfoundland. The major rock types present are; felsic gneisses in the west, anorthositic rocks in the southwest, semipelitic to psammitic schists in the east, and granitic intrusions within the gneisses. Mafic dykes intrude the gneisses, but are unknown within the schists. Finally, west of the Grand Lake Thrust but included within the map area, are limestones and phyllites of the west Newfoundland carbonate terrane. -- The limestones and phyllites occur in the western part of the map area, west of the Grand Lake Thrust. They are deformed, and vary from unmetamorphosed to mildly metamorphosed( chlorite zone of the greenschist facies). -- The felsic gneisses locally contain granulite facies mineral assemblages, but are everywhere affected by later retrograde metamorphism that increases in intensity from greenschist to amphibolite facies, from west to east. The mafic dykes intruding the gneisses exhibit the same effects of later metamorphism. The metamorphic change is accompanied by increasing intensity of deformation from west to east across the area. -- The semipelitic to psammitic schists are confined to the eastern part of the area, where they exhibit upper greenschist to amphibolite facies mineral assemblages. These rocks are polydeformed and faulted against the gneisses to the west. -- The granitic intrusions occur within the gneisses only. They contain no evidence of the early granulite facies metamorphic event present in the host gneisses, and are for the most part massive. -- The gneissic rocks are interpreted as Grenvillian inliers (basement), and are correlated with similar rocks of the Grenvillian Indian Head Complex,nearby to the west. The limestones, phyllites, and polydeformed schists are interpreted as a cover sequence affected by Paleozoic deformation, which also involved the basement gneisses and mafic dykes. The granitic bodies are interpreted as later intrusions, possibly related to Taconic or Acadian orogenesis. The stratigraphic and orogenic development of the area can be related to the formation of the Late Precambrian continental margin of eastern North America, and its Paleozoic destruction

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

International audienc

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