Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Objective

The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.

Methods

In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7).

Results

A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases.

Conclusions

These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.     

Climate change in the Seychelles: implications for water and coral reefs

The Seychelles is a small island state in the western Indian Ocean that is vulnerable to the effects of climate change. This vulnerability led the Intergovernmental Panel on Climate Change (IPCC) in 2001 to express concern over the potential economic and social consequences that may be faced by small island states. Small island states should be prepared to adapt to such changes, especially in view of their dependence on natural resources, such as water and coral reefs, to meet basic human welfare needs. Analysis of long-term data for precipitation, air temperature, and sea-surface temperature indicated that changes are already observable in the Seychelles. The increase in dry spells that resulted in drought conditions in 1999 and the 1998 mass coral bleaching are indicative of the events that are likely to occur under future climate change. Pre-IPCC Third Assessment Report scenarios and the new SRES scenarios are compared for changes in precipitation and air surface temperature for the Seychelles. These intercomparisons indicate that the IS92 scenarios project a much warmer and wetter climate for the Seychelles than do the SRES scenarios. However, a wetter climate does not imply readily available water, but rather longer dry spells with more intense precipitation events. These observations will likely place enormous pressures on water-resources management in the Seychelles. Similarly, sea-surface temperature increases predicted by the HADCM3 model will likely trigger repeated coral-bleaching episodes, with possible coral extinctions within the Seychelles region by 2040. The cover of many coral reefs around the Seychelles have already changed, and the protection of coral-resilient areas is a critical adaptive option.     

All-in-one whole exome sequencing strategy with simultaneous copy number variant,single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience

Objective

We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods

After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

Results

In total, 415 prenatal samples were included. Following a non-causative QF-PCR result, WES-CNV analysis was initially requested for 74.3% of the chorionic villus (CV) samples and 45% of the amniotic fluid (AF) samples. In case WES-CNV analysis did not reveal a causative aberration, SNV-re-analysis was requested in 41.7% of the CV samples and 17.5% of the AF samples. All initial analyses could be finished within 2 weeks after sampling. For SNV-re-analysis during pregnancy, turn-around-times (TATs) varied between one and 8 days.

Conclusion

We show a highly efficient all-in-one WES-based strategy, with short TATs, and the option of rapid SNV-re-analysis after a normal CNV result.     

东非地区人类活动的负面影响:全球国际水域分析研究

本文分析了在陆地与海洋相交的界面上人类活动与环境之间的复杂关系,重点是全球国际水域评估(GIWA)框架下的两个亚区:索马里洋流亚区(东非)和印度洋岛屿国家亚区.     

The negative impacts of human activities in the eastern African region: an international waters perspective

The complex interactions between human activities and the environment at the interface of land and water is analyzed with a focus on the Somali Current (East Africa), and Indian Ocean Island States, subregions of the Global International Waters Assessment (GIWA). These 2 subregions contain some of the world's richest ecosystems, including the high biodiversity forests of Madagascar and the diverse coastal habitats of the eastern African coast. These ecosystems support local communities and national and regional economies. Current and future degradation of these systems, from water basins to continental shelves, affects the livelihoods and sustainability of the countries in the region, and long-term efforts to reduce poverty. The assessments determined that pollution and climate change are the primary environmental and social concerns in the Islands of the Indian Ocean, while freshwater shortage and unsustainable exploitation of fisheries and other living resources are the primary environmental and social concerns in East Africa. The GIWA approach, through assessing root causes of environmental concerns, enables the development of policy approaches for mitigating environmental degradation. This paper explores policy frameworks for mitigating the impacts, and reducing the drivers, of 3 environmental concerns--freshwater shortage; solid waste pollution; and climate change--addressing social and institutional causes and effects, and linking the subregions to broad international frameworks. The common theme in all 3 case studies is the need to develop integrated ecosystem and international waters policies, and mechanisms to manage conflicting interests and to limit threats to natural processes.