Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 OAS1 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of OAS1. We suggest that genetically-regulated loss of OAS1 expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the OAS1 risk haplotypes.

A masculinizing supergene underlies an exaggerated male reproductive morph in a spider

In many species, individuals can develop into strikingly different morphs, which are determined by a simple Mendelian locus. How selection shapes loci that control complex phenotypic differences remains poorly understood. In the spider Oedothorax gibbosus, males either develop into a ‘hunched’ morph with conspicuous head structures or as a fast developing ‘flat’ morph with a female-like appearance. We show that the hunched-differs from the flat-determining allele by a hunch-specific genomic fragment of approximately 3 megabases. This fragment comprises dozens of genes that duplicated from genes found at different chromosomes. All functional duplicates, including doublesex - a key sexual differentiation regulatory gene, show male-specific expression, which illustrates their combined role as a masculinizing supergene. Our findings demonstrate how extensive indel polymorphisms and duplications of regulatory genes may contribute to the evolution of co-adapted gene clusters, sex-limited reproductive morphs, and the enigmatic evolution of exaggerated sexual traits in general.

The US CDC RT-PCR probes for the Wuhan 2019-nCoV are non-specific for SARS - there is a better non-specific 500bp option (21852-22427) within the spike-protein

The World Health Organization has declared the Wuhan coronavirus [1–3] outbreak a public health emer- gency on 30th Jan, 2020. An accurate detection of the Wuhan virus is imperative to avoid false positives, since 2019-nCoV [2,3] shares significant homology [4] with other species.On the 24th of Jan, the CDC has published a list of 3 probes (Fig 1) for detecting the 2019-nCoV. Detection of all three probes would give a positive result, while detection of one or two gives an ’inconclusive result’ (and obviously negative when none are found).All 3 probes will have significant homology in other strains (Table 1 and Fig 2 ) - specifically SARS (Severe Acute Respiratory Syndrome). A much more specific option is to look within a 500bp genomic fragment in the N-terminal of the spike protein (Accid:NC 045512.2 [2],21852-22427, SI.cdc:nCoVFULLSLICE.fa), which seems to the most perturbed in this virulent strain [5].It is also important to have a common repository for all countries to be following a similar protocol. Many papers do no provide what PCR was used to detect coronaviruses [6].

Ubiquitous genomic fragment in human 2019-nCoV viruses in the spike-protein, also encoding a novel 87 aa protein, completely missing in all other coronaviruses

The origins of the highly virulent coronavirus isolated from Wuhan (Hubei, China) are uncertain, as are the reasons for its highly virulent nature (human-to-human transmission before the onset of symptoms). Here, 29 genomes of 2019-nCoV in GISAID reveals a genomic fragment which is present in all 2019-nCoV genomes, (and also in the recent Nanopore sequencing data from a family [1]), and absent in other species. The only entry in GISAID from bats (BatCoV-RaTG13) is a mystery (it does not have any publications linked to it), but is very close to human 2019-nCoV. Mutations in the viral genome need to translate in changes in protein sequences (and function) in order modulate its virulence. This genomic fragment is in the N-terminal of the spike-protein (98-228), a known-epitope region and implicated in viral entry into host cells. Interestingly, this region also encodes a novel 87 novel protein, with a shifted open-reading frame (a phenomenon common in viruses). The genomic fragment will help in faster diagnosis (excluding all other coronaviruses), while the protein information will aid in vaccine or inhibitor design. Note, there are no other fragments which have this property - present in nCov and absent in others. Coincidentally, amino acids ‘17-240 were deleted from the N-terminal domain of the TGEV Spike gene’ using CRISPR, an experiment carried out in Wuhan [2].

Genomic Alterations of Staphylococcus aureus ATCC 25923 after Prolonged Passage in the Laboratory

Staphylococcus aureus reference strain ATCC 25923 has been maintained for more than a decade in our laboratory. Genomic study revealed that the resulting strain AFIPCBER_B_8.4 has lost a 37-kb genomic fragment of the ATCC 25923 parental strain.