A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound

Objective

Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.

Methods

We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes.

Results

We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.

Conclusion

Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.     

Bewertungsmaßstäbe für die biologische Vielfalt

The main objective of the UN Convention on Biological Diversity is the global conservation of biological diversity. As biological diversity is utilised — directly or indirectly — as a resource for human needs, this utilisation has to be made sustainable. The elaboration of adequate protection and utilisation concepts requires suitable evaluation criteria to measure sustainability. For the sector of environmental protection, the Federal Environmental Agency has carried out a study to determine the criteria which are currently used in different areas. This study (review and evaluation) covers not only the criteria themselves, but also includes additional information such as the underlying principles. Biodiversity as an autonornous area of protection has been addressed in only quite a few papers up to now. However, there already exists a range of criteria which are relevant for biodiversity. But at the same time many gaps’ and inconsistencies were identified which have to be eliminated in cooperation with other policy sectors to obtain a basis for the above-mentioned protection and utilisation concepts.     

Mental representations of animal and plant species in their social contexts: Results from a survey across Europe

Despite a growing body of literature on public views on biodiversity and nature, our understanding of public attitudes towards animal and plant species is still rudimentary. This study investigates mental representations, constituted by beliefs, of three types of species (a large mammal, a spider and a non-native plant), and explores their links with cultural factors such as value orientations and cultural capital, in order to better understand attitudes towards these species.We conducted a survey in eight sites across Europe (n = 2378) and found strong relationships between beliefs about species, in particular with regard to their harmlessness, value and previous population change, and the desirability of an increase in this species. Other beliefs, such as perceived nativeness, were less influential. We discuss how respondents combined beliefs to mental representations of species, and show how representations are related to species-independent factors that tap respondents’ cultural context, such as socially shared value orientations and education.     

Influence of grain size on species-habitat models

High resolution remote sensing data facilitate the use of small-scale habitat features such as trees or hedges in the analysis of species-habitat relationships. Such data potentially enable more accurate species-habitat mapping than lower resolution data. Here, for the first time, we systematically investigated this hypothesis by altering the spatial resolution from 1 m up to 1000 m grain size in species-habitat models of 13 bird species. The study area covered the Nidda river catchment in central Germany, a large heterogeneous landscape of 1620 km². A high resolution habitat map of the area was converted to coarser spatial and thematic resolutions in seven steps. We investigated how model performance responded to grain size, and we compared the differential effects of spatial resolution and thematic resolution on model performance. Explained deviance (D²) of the bird models generally decreased with coarser spatial resolution of the data, although it did not decrease monotonically in all species. On average across all species, model D² decreased from 41.5 at 1 m grain size to 15.9 at 1000 m grain size. Ten species were best modelled at 1 m, two species at 3 m and one species at 32 m grain size. Model performance degraded continuously with increasing grain size, both in habitat generalist and habitat specialist bird species, and was systematically lower in habitat generalists. The higher model performance observed at finer grain sizes was most likely caused by the combination of three factors: (1) high spatial accuracy of bird records and (2) a more precise location and delineation of habitat features and, (3) to a lesser degree, by more habitat types differentiated in maps of finer resolution. We conclude that higher spatial and thematic resolution data can be essential for deriving accurate predictions on bird distribution patterns from species-habitat models. Especially for bird species that are sensitive to specific land-use types or to small-scaled habitat features, a grain size of 1-3 m seems most promising.     

Tissue heavy metal concentrations of stranded California sea lions (Zalophus californianus) in Southern California

Concentrations of nine heavy metals (As, Cd, Cu, Fe, Hg, Pb, Mn, Mo and Zn) were determined in the hepatic and renal tissues of 80 stranded California sea lions (Zalophus californianus). Significant age-dependant increases were observed in liver and kidney concentrations of cadmium and mercury, and renal zinc concentrations. Hepatic iron concentrations were significantly higher in females than males. Animals with suspected domoic acid associated pathological findings had significantly higher concentrations of liver and kidney cadmium; and significantly higher liver mercury concentrations when compared to animals classified with infectious disease or traumatic mortality. Significantly higher hepatic burdens of molybdenum and zinc were found in animals that died from infectious diseases. This is the largest study of tissue heavy metal concentrations in California sea lions to date. These data demonstrate how passive monitoring of stranded animals can provide insight into environmental impacts on marine mammals.     

Potential Effects of Direct Transfer Payments on Farmland Habitat Diversity in a Marginal European Landscape

Farmland habitat diversity in marginal European landscapes changed significantly in the past decades. Further changes toward homogenization are expected, particularly in the course of European agricultural policy. Based on three alternative transfer payment schemes, we modeled spatially explicit potential effects on the farmland habitat diversity in a marginal European landscape. We defined (1) a scenario with direct transfer payments coupled to production, (2) a scenario with direct transfer payments decoupled from production, and (3) a scenario phasing out all direct transfer payments. We characterized habitat diversity with three indices: habitat richness, evenness, and rarity. The habitat pattern in 1995 served as reference for comparison. All scenarios predicted a general trend of homogenization of the farmland habitat pattern, yet to a differing extent. Transfer payments coupled to production (Scenario 1) favored the abandonment of agricultural production, particularly in low-productive areas and arable land use in more productive areas. Habitat richness and habitat evenness had intermediate values in this scenario. Decoupling transfer payments from production (Scenario 2) supported grassland as most profitable farming system. This led to a grassland-dominated landscape with low values of all habitat diversity indices. Phasing out transfer payments (Scenario 3) resulted in complete abandonment or afforestation of agricultural land and extremely low values in all habitat diversity indices. Scenario results indicate that transfer payments may prevent cessation of agricultural production, but may not counteract homogenization in marginal landscapes. Conserving high farmland habitat diversity in such landscapes may require support schemes, e.g., Pillar Two of EU Common Agricultural Policy.     

Gehalte an polycyclischen aromatischen Kohlenwasserstoffen (PAK) in Oberböden Hamburgs

The contents of 19 polycyclic aromatic hydrocarbons (PAH) in topsoil samples from 108 sites within the territory of the federal state of Hamburg were analyzed. The investigation was performed to provide a view on background values in the metropolitan area and the influence of land use on PAH in soils. Known contaminated sites were not included in the investigation. Values in the area ranged from 0.1 to 44.3 mg/kg d.m. with a median of 3.6. 80% of the measurements were below 10 mg/kg d.m. Contents decreased strongly with a growing distance from the city’s center. The median is 4.4 mg/kg d.m. in the center, 1.3 in the rural periphery (marsh) and 0.4 mg/kg d.m. in preweichselian uplands (“geest”). PAH contaminations originate from diffuse atmospheric emissions caused by car traffic and room heating, but also by war damages which lead to widespread burnings and consequently to the widespread dispersion of remains. The contents measured are in the range of published values from other densely populated areas, although a comparatively comprehensive investigation from another region does not exist.     

Two unbalanced segregation products due to a maternal t(7;16)inv(16)

We report a prenatal case of a maternally inherited abnormal chromosome 16, originally interpreted as a pericentric inversion only, but after family studies re-interpreted as a pericentric inversion (16) accompanied by an unbalanced (7;16) translocation. Because of the inversion 16 and an elder son with developmental delay and craniofacial dysmorphic features, in the past karyotyped as 46,XY, the chromosomes 16 of the mother and son were carefully re-examined. Using a whole chromosome 16 paint and sub-telomere probes of 16p and 16q, the karyotype of the mother was shown to be 46,XX,inv(16)(p11.2q23.2).ish t(7;16)(q36;p13.3)inv(16). Subsequently one chromosome 16 of the elder son appeared to be a der(16)t(7;16)(q36;p13.3). This is probably the result of a meiotic crossover between the chromosomes 16 in the mother. The prenatal karyotype was finally interpreted as 46,XY,inv(16)(p11.2q23.2).ish der(16)t(7;16)(q36;p13.3)inv(16). This is the same cytogenetic imbalance as his elder brother: a partial trisomy of chromosome 7 (q36→qter) and a partial monosomy of chromosome 16 (p13.3→pter). Copyright © 2001 John Wiley & Sons, Ltd.