Prioritizing taxa for genetic reference database development to advance inland water conservation

Biodiversity loss has accelerated over the past century and freshwater species overall are among those experiencing greatest declines. Genetic resources have the potential to help evaluate the full magnitude of this loss and represent a key tool to effectively allocate conservation resources and monitor the success of restoration efforts. The full power of genetic resources will be realized when the daunting task of referencing all DNA sequences of freshwater organisms is complete. Here, we quantified the availability and distribution of barcode and genome data for freshwater macroscopic organisms in Canada, a country rich in inland water resources and thus particularly vulnerable to aquatic species losses. Impressively, most inland water species (86 %) were represented by barcodes recorded in the BOLD Systems database, while very few had full genomes available (<4 %) in the NCBI database. We identified barcode data deficiencies in northern regions and for taxa assessed as most at risk or without sufficient information for conservation status classification. As expected, the speciose insect group had a lower-than-average number of records per species and a high proportion of data deficient species without adequate barcode coverage. This study highlights where future sequencing resources should be prioritized within initiatives such as the Canada BioGenome Project and BIOSCAN Canada and provides a workflow that could be applied internationally to inform conservation management plans and to mitigate biodiversity loss

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

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

Erratum: A Case of Xanthoma Disseminatum with Spontaneous Resolution over 10 Years: Review of the Literature on Long-Term Follow-Up

Xanthoma disseminatum (XD) is a rare and potentially progressive non-Langerhans-cell histiocytosis. To date, a few cases of XD with spontaneous complete resolution have been described. The present report describes a 16-year-old girl who presented with yellow to red-brown papules and nodules on her eyelids, cheeks, axillae, back and buttocks. Indirect laryngoscopy showed multiple xanthomatous plaques on the larynx, posterior pharynx, epiglottis, and vocal cords. Additional findings were polyuria, polydipsia, and amenorrhea. Skin biopsy and electron microscopy results confirmed the diagnosis of XD. The patient was treated with fenofibrate, simvastatin, desmopressin, and sex-hormone replacement therapy. Her skin lesions began to slowly fade 6 years after disease onset, eventually resolving spontaneously and completely, but leaving an atrophic scar, frank anetoderma, and persisting diabetes insipidus. This case report together with a review of the English-language literature on the long-term follow-up of XD patients provides additional information on the natural history of this disease