Comprehensive prenatal diagnostics: Exome versus genome sequencing

Objective

This study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies with fetal anomalies by comparing the results with conventional chromosomal microarray (CMA) analysis.

Methods

A total of 40 pregnancies with fetal anomalies or increased nuchal translucency (NT ≥ 5 mm) were included between the 12th and 21st week of gestation. Trio WES/WGS and CMA were performed in all cases.

Results

The trio WES/WGS analysis increased the diagnostic yield by 25% in cases with negative CMA results. Furthermore, all six chromosomal aberrations identified by CMA were independently detected by WES/WGS analysis. In total, 16 out of 40 cases obtained a genetic sequence variant, copy number variant, or aneuploidy explaining the phenotype, resulting in an overall WES/WGS diagnostic yield of 40%. WES analysis provided a more reliable identification of mosaic sequence variants than WGS because of its higher sequencing depth.

Conclusions

Prenatal WES/WGS proved to be powerful diagnostic tools for fetal anomalies, surpassing the diagnostic yield of CMA. They have the potential to serve as standalone methods for prenatal diagnosis. The study highlighted the limitations of WGS in accurately detecting mosaic variants, which is particularly relevant when analyzing chorionic villus samples.     

Heavy metals and pesticides in anuran spawn and tadpoles,water, and sediment

High concentrations of metals (cadmium, copper, lead, and zinc) and of lindane were measured in the sediment and in the spawn and tadpoles of Bufo bufo, Rana dalmatina, and Rana ridibunda from two Austrian locations. Residues in spawn suggest maternal transfer. Increase of the metal concentrations from spawn to advanced tadpole stage is explained by the larval microphaguous feeding habits which cause high exposition of the tadpoles to substances concentrating in sediments and suspended particles. Metal and pesticide concentrations in spawn and tadpoles are toxic to various other aquatic organisms and are furthermore considered to be potentially hazardous to the anurans themselves. The results are conform with world‐wide observations of contamination of anuran larvae with heavy metals, and prove the significance of non‐point source chemical exposure due to allochthonous toxicant input by wind load and precipitation.     

Pleasure Boatyard Soils are Often Highly Contaminated

The contamination in pleasure boatyards has been investigated. Measured concentrations of copper, zinc, lead, mercury, cadmium, tributyltin (TBT), the 16 most common polycyclic aromatic hydrocarbons (∑16 PAHs), and the seven most common polychlorinated biphenyls (∑7 PCBs) from investigations at 34 boatyards along the Swedish coast have been compiled. The maximum concentrations were 7,700 for Cu, 10,200, for Zn, 40,100 for Pb, 188 for Hg, 18 for Cd, 107 for TBT, 630 for carcinogenic PAHs, 1,480 for ∑16 PAHs, and 3.8 mg/kg DW for ∑7 PCB; all 10–2,000 higher than the Swedish environmental qualitative guidelines. In addition, the mean of the median values found at the 34 places shows that the lower guidance value for sensitive use of land was exceeded for the ∑7 PCBs, carcinogenic PAHs, TBT, Pb, Hg, and Cu by a factor of 380, 6.8, 3.6, 2.9, 2.2 and 1.7, respectively. The even higher guideline value for industrial use was exceeded for the ∑7 PCBs and TBT by a factor of 15 and 1.8, respectively. TBT, PAHs, Pb, Cd, and Hg are prioritized substances in the European Water Framework Directive and should be phased out as quickly as possible. Because of the risk of leakage from boatyards, precautions should be taken. The high concentrations measured are considered to be dangerous for the environment and human health and highlight the urgent need for developing and enforcing pleasure boat maintenance guidelines to minimize further soil and nearby water contamination.     

Effect of sulfide on the cytotoxicity of arsenite and arsenate in human hepatocytes (HepG2) and human urothelial cells (UROtsa)

Arsenic, a common poison, is known to react with sulfide in vivo, forming thioarsenates. The acute toxicity of the inorganic thioarsenates is currently unknown. Our experiments showed that a fourfold sulfide excess reduced acute arsenite cytotoxicity in human hepatocytes (HepG2) and urothelial cells (UROtsa) significantly, but had little effect on arsenate toxicity. Speciation analysis showed immediate formation of thioarsenates (up to 73 % of total arsenic) in case of arsenite, but no speciation changes for arsenate. Testing acute toxicity of mono- and trithioarsenate individually, both thioarsenates were found to be more toxic than their structural analogue arsenate, but less toxic than arsenite. Toxicity increased with the number of thio groups. The amount of cellular arsenic uptake after 24 h corresponded to the order of toxicity of the four compounds tested. The dominant to almost exclusive intracellular arsenic species was arsenite. The results imply that thiolation is a detoxification process for arsenite in sulfidic milieus. The mechanism could either be that thioarsenates regulate the amount of free arsenite available for cellular uptake without entering the cells themselves, or, based on their chemical similarity to arsenate, they could be taken up by similar transporters and reduced rapidly intracellularly to arsenite.     

Application of a spatial meta-population model with stochastic parameters to the management of the invasive grass Nassella trichotoma in North Canterbury, New Zealand

Optimising the management of invasive plants requires the identification of the population size outcomes for alternative management strategies. Mathematical models can be useful tools for making such management strategy comparisons. In this paper we develop a generic landscape meta-population model and apply it to the weedy grass, Nassella trichotoma, an invasive species occupying approximately 800 land parcels, predominantly pastoral farms, in the Hurunui district, North Canterbury, New Zealand. Empirical evidence reveals that this meta-population is currently stable (at a median density of 6 plants ha⁻¹) under a community strategy requiring manual removal (termed ‘grubbing’) of plants annually from all land parcels. Reduction in population size requires an alternative management strategy. Field data, collected over a 12 year period, were used to provide stochastic parameter values for land parcel size, carrying capacity, rates of local population growth and grubbing.The model reveals that at steady state, the most significant contribution to population growth on a land parcel comes from within the land parcel itself; the expected annual per capita growth on an individual land parcel is 4 orders of magnitude greater than the expected annual contribution from plants arising from other land parcels. This result implies that many of the farms currently supporting N. trichotoma may pose little or no threat to, nor are threatened themselves by, other farms infested by the weed. However, the steady state distribution (of the weed's population density) was sensitive to the spread rate, revealing a need for data on this process. It was also sensitive to how any increase in the grubbing rate is distributed; increasing it via a uniform distribution U(0, 1) where all rates between 0 and 100% year⁻¹ are equally probable did not affect the steady state, whereas increasing the rates via the uniform distribution U(0.25, 0.75) resulted in fewer farms with high population densities. In general the model provides a basis for exploring the effects of a wide range of alternative grubbing strategies on population growth in N. trichotoma.     

“My Husband Usually Makes Those Decisions”: Gender,Behavior, and Attitudes Toward the Marine Environment

Human behavior impacts the environment we live in. In order to better understand how one group, boat owners, in three Nordic countries adjacent to the Baltic Sea; Sweden, Finland and Denmark, viewed the relationship between the marine environment, leisure boats and issues of responsibility, a survey study was conducted (n = 1701). The results show that there are differences between gender in many areas and those women in general are more environmentally friendly than men in their views and behavior. Men and women seek information about boating by different channels and this knowledge may be used in future information campaigns. Both men and women ranked boat owners as having the lowest impact on the marine environment and perceived these to be responsible for addressing environmental issues caused by leisure boat activities. The results also show that it is important to prove the effectiveness of an environmentally safe product since this factor is ranked higher than price when considering buying a product. The results suggest that once environmentally friendly behavior is established, such as recycling, this behavior continues. One implication of this study is that small changes in human behavior are seen as acceptable but larger commitments are more difficult to achieve. If individuals do not feel responsible for causing environmental damage, this aspect needs to be addressed in information aimed at this group. Novel approaches on framing the information and new ways of disseminating information are needed.     

Understanding the sources and effects of abandoned,lost, and discarded fishing gear on marine turtles in northern Australia

Globally, 6.4 million tons of fishing gear are lost in the oceans annually. This gear (i.e., ghost nets), whether accidently lost, abandoned, or deliberately discarded, threatens marine wildlife as it drifts with prevailing currents and continues to entangle marine organisms indiscriminately. Northern Australia has some of the highest densities of ghost nets in the world, with up to 3 tons washing ashore per kilometer of shoreline annually. This region supports globally significant populations of internationally threatened marine fauna, including 6 of the 7 extant marine turtles. We examined the threat ghost nets pose to marine turtles and assessed whether nets associated with particular fisheries are linked with turtle entanglement by analyzing the capture rates of turtles and potential source fisheries from nearly 9000 nets found on Australia's northern coast. Nets with relatively larger mesh and smaller twine sizes (e.g., pelagic drift nets) had the highest probability of entanglement for marine turtles. Net size was important; larger nets appeared to attract turtles, which further increased their catch rates. Our results point to issues with trawl and drift‐net fisheries, the former due to the large number of nets and fragments found and the latter due to the very high catch rates resulting from the net design. Catch rates for fine‐mesh gill nets can reach as high as 4 turtles/100 m of net length. We estimated that the total number of turtles caught by the 8690 ghost nets we sampled was between 4866 and 14,600, assuming nets drift for 1 year. Ghost nets continue to accumulate on Australia's northern shore due to both legal and illegal fishing; over 13,000 nets have been removed since 2005. This is an important and ongoing transboundary threat to biodiversity in the region that requires attention from the countries surrounding the Arafura and Timor Seas. Entender las Fuentes y Efectos de Equipo de Pesca Abandonado, Perdido y Desechado sobre las Tortugas Marinas del Atlántico Norte     

Herbicides: A new threat to the Great Barrier Reef

The runoff of pesticides (insecticides, herbicides and fungicides) from agricultural lands is a key concern for the health of the iconic Great Barrier Reef, Australia. Relatively low levels of herbicide residues can reduce the productivity of marine plants and corals. However, the risk of these residues to Great Barrier Reef ecosystems has been poorly quantified due to a lack of large-scale datasets. Here we present results of a study tracing pesticide residues from rivers and creeks in three catchment regions to the adjacent marine environment. Several pesticides (mainly herbicides) were detected in both freshwater and coastal marine waters and were attributed to specific land uses in the catchment. Elevated herbicide concentrations were particularly associated with sugar cane cultivation in the adjacent catchment. We demonstrate that herbicides reach the Great Barrier Reef lagoon and may disturb sensitive marine ecosystems already affected by other pressures such as climate change.