DEVELOPING NEW APPROACHES TO GLOBAL STOCK STATUS ASSESSMENT AND FISHERY PRODUCTION POTENTIAL OF THE SEAS

Stock status is a key parameter for evaluating the sustainability of fishery resources and developing corresponding management plans. However, the majority of stocks are not assessed, often as a result of insufficient data and a lack of resources needed to execute formal stock assessments. The working group involved in this publication focused on two approaches to estimating fisheries status: one based on single-stock status, and the other based on ecosystem production.JRC.G.4-Maritime affair

Assessment for All initiative(a4a) - Workshop on development of MSE algorithms with R/FLR/a4a

The a4a approach to Management Strategies Evaluation ( MSE ) is to develop a set of common methods and procedures to build a minimal standard MSE algorithm. This has the most common elements of both uncertainty and management options. Such a tool set should allow for the development of MSE simulations for many fisheries in an operational time frame. Between the 30th of January and the 3rd of February, in Ispra, Italy, the JRC organized a workshop on development of MSE algorithms with R/FLR/a4a. The workshop was a mix of hands-on coding and discussion/implementation of concepts associated with MSEs. The participants used the most recent version of the a4a MSE code, modularized the most important processes and developed their own version of several processes so that the MSE could model and test alternative management procedures to the one initially coded.JRC.D.2-Water and Marine Resource

Improving estimates of population status and trend with superensemble models

Fishery managers must often reconcile conflicting estimates of population status and trend. Superensemble models, commonly used in climate and weather forecasting, may provide an effective solution. This approach uses predictions from multiple models as covariates in an additional "superensemble" model fitted to known data. We evaluated the potential for ensemble averages and superensemble models (ensemble methods) to improve estimates of population status and trend for fisheries. We fit four widely applicable data-limited models that estimate stock biomass relative to equilibrium biomass at maximum sustainable yield (B/BMSY). We combined these estimates of recent fishery status and trends in B/BMSY with four ensemble methods: an ensemble average and three superensembles (a linear model, a random forest and a boosted regression tree). We trained our superensembles on 5,760 simulated stocks and tested them with cross-validation and against a global database of 249 stock assessments. Ensemble methods substantially improved estimates of population status and trend. Random forest and boosted regression trees performed the best at estimating population status: inaccuracy (median absolute proportional error) decreased from 0.42 -0.56 to 0.32 -0.33, rank-order correlation between predicted and true status improved from 0.02 - 0.32 to 0.44 - 0.48 and bias (median proportional error) declined from - 0.22 - 0.31 to - 0.12 - 0.03. We found similar improvements when predicting trend and when applying the simulation-trained superensembles to catch data for global fish stocks. Superensembles can optimally leverage multiple model predictions; however, they must be tested, formed from a diverse set of accurate models and built on a data set representative of the populations to which they are applied

Genotype-phenotype correlation at codon 1740 ofSETD2

The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual-function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α-tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan-Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2

Estimating Trends of Population Decline in Long-Lived Marine Species in the Mediterranean Sea Based on Fishers' Perceptions

We conducted interviews of a representative sample of 106 retired fishers in Italy, Spain and Greece, asking specific questions about the trends they perceived in dolphin and shark abundances between 1940 and 1999 (in three 20 year periods) compared to the present abundance. The large marine fauna studied were not target species of the commercial fleet segment interviewed (trawl fishery). The fishers were asked to rank the perceived abundance in each period into qualitative ordinal classes based on two indicators: frequency of sightings and frequency of catches (incidental or intentional) of each taxonomic group. The statistical analysis of the survey results showed that both incidental catches and the sighting frequency of dolphins have decreased significantly over the 60+ years of the study period (except for in Greece due to the recent population increase). This shows that fishers' perceptions are in agreement with the declining population trends detected by scientists. Shark catches were also perceived to have diminished since the early 1940s for all species. Other long-lived Mediterranean marine fauna (monk seals, whales) were at very low levels in the second half of the 20th century and no quantitative data could be obtained. Our study supports the results obtained in the Mediterranean and other seas that show the rapid disappearance (over a few decades) of marine fauna. We show that appropriately designed questionnaires help provide a picture of animal abundance in the past through the valuable perceptions of fishers. This information can be used to complement scientific sources or in some cases be taken as the only information source for establishing population trends in the abundance of sensitive species

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

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

Disrupted autophagy undermines skeletal muscle adaptation and integrity

This review assesses the importance of proteostasis in skeletal muscle maintenance with a specific emphasis on autophagy. Skeletal muscle appears to be particularly vulnerable to genetic defects in basal and induced autophagy, indicating that autophagy is co-substantial to skeletal muscle maintenance and adaptation. We discuss emerging evidence that tension-induced protein unfolding may act as a direct link between mechanical stress and autophagic pathways. Mechanistic links between protein damage, autophagy and muscle hypertrophy, which is also induced by mechanical stress, are still poorly understood. However, some mouse models of muscle disease show ameliorated symptoms upon effective targeting of basal autophagy. These findings highlight the importance of autophagy as therapeutic target and suggest that elucidating connections between protein unfolding and mTOR-dependent or mTOR-independent hypertrophic responses is likely to reveal specific therapeutic windows for the treatment of muscle wasting disorders

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes