The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Exploring the Use of Ecosystem Services Conceptual Models to Account for the Benefits of Public Lands: An Example from National Forest Planning in the United States

A shared understanding of the benefits and tradeoffs to people from alternative land management strategies is critical to successful decision-making for managing public lands and fostering shared stewardship. This study describes an approach for identifying and monitoring the types of resource benefits and tradeoffs considered in National Forest planning in the United States under the 2012 Planning Rule and demonstrates the use of tools for conceptualizing the production of ecosystem services and benefits from alternative land management strategies. Efforts to apply these tools through workshops and engagement exercises provide opportunities to explore and highlight measures, indicators, and data sources for characterizing benefits and tradeoffs in collaborative environments involving interdisciplinary planning teams. Conceptual modeling tools are applied to a case study examining the social and economic benefits of recreation on the Ashley National Forest. The case study illustrates how these types of tools facilitate dialog for planning teams to discuss alternatives and key ecosystem service outcomes, create easy to interpret visuals that map details in plans, and provide a basis for selecting ecosystem service (socio-economic) metrics. These metrics can be used to enhance environmental impact analysis, and help satisfy the goals of the National Environmental Policy Act (NEPA), the 2012 Planning Rule, and shared stewardship initiatives. The systematic consideration of ecosystem services outcomes and metrics supported by this approach enhanced dialog between members of the Forest planning team, allowed for a more transparent process in identification of key linkages and outcomes, and identified impacts and outcomes that may not have been apparent to the sociologist who is lacking the resource specific expertise of these participants. As a result, the use of the Ecosystem Service Conceptual Model (ESCM) process may result in reduced time for internal reviews and greater comprehension of anticipated outcomes and impacts of proposed management in the plan revision Environmental Impact Statement amongst the planning team

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed