Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Modelling effects of time-variable exposure to the pyrethroid beta-cyfluthrin on rainbow trout early life stages

Abstract Background Available literature and regulatory studies show that the severity of effects of beta-cyfluthrin (a synthetic pyrethroid) on fish is influenced by the magnitude and duration of exposure. To investigate how the exposure pattern to beta-cyfluthrin (constant vs peak) may influence the response of the fish, we used a mechanistic effect model to predict the survival and growth of the rainbow trout over its early life stages (i.e. egg, alevin and swim-up fry). We parameterized a toxicokinetic–toxicodynamic (TKTD) module in combination with a dynamic energy budget model enabling us to describe uptake and elimination, as well as to predict the threshold concentration for survival and sublethal effects (feeding behaviour and growth). This effect model was calibrated using data from an early life stage experiment where trout was exposed to a constant concentration of cyfluthrin. The model was validated by comparing model predictions to independent data from a pulsed-exposure study with early life stages of rainbow trout. Results The co-occurrence of effects on behaviour and growth raised the possibility that these were interrelated, i.e. impairment of feeding behaviour may have led to reduced food intake and slower growth. We, therefore, included ‘effect on feeding’ as mode of action in the TKTD module. At higher concentrations, the constant exposure led to death. The model was able to adequately capture this effect pattern in the calibration. The model was able to adequately predict the response of fish eggs, alevins and swim-up fry, from both the qualitative (response pattern) and quantitative points of view. Conclusions Since the model was successfully validated, it can be used to predict survival and growth of early life stages under various realistic time-variable exposure profiles (e.g. profiles from FOCUS surface water modelling) of beta-cyfluthrin

Dynamic energy budgets in population ecotoxicology : applications and outlook

Most of the experimental testing in ecotoxicology takes place at the individual level, but the protection goals for environmental risk assessment are at the population level (or higher). Population modelling can fill this gap, but only models on a mechanistic basis allow for extrapolation beyond the conditions in the experimental tests. The life-history traits of individuals form the basis of population dynamics, and population modelling thus requires a proper understanding of the individual's behaviour. The dynamic energy budget (DEB) theory offers a flexible platform for the development of models at the individual level. Linking DEB models to population models can thus provide a mechanistic basis for extrapolation. Here, we provide a conceptual overview of DEB theory, with emphasis on its applications in ecotoxicology. Furthermore, we briefly review the applications in which a DEB-based individual model has been linked to structured population dynamics. Finally, we discuss some of the most important areas for further research in this context. © 2013 Elsevier B.V

Juvenile food limitation in standard tests: a warning to ecotoxicologists.

Standard ecotoxicological tests are as simple as possible and food sources are mainly chosen for practical reasons. Since some organisms change their food preferences during the life-cycle, they might be food limited at some stage if we do not account for such a switch. As organisms tend to respond more sensitively to toxicant exposure under food limitation, the interpretation of test results may then be biased. Using a reformulation of the von Bertalanffy model to analyze growth data of the pond snail Lymnaea stagnalis, we detected food limitation in the early juvenile phase. The snails were held under conditions proposed for a standardized test protocol, which prescribes lettuce as food source. Additional experiments showed that juveniles grow considerably faster when fed with fish flakes. The model is based on Dynamic Energy Budget (DEB) theory, which allows for mechanistic interpretation of toxic effects in terms of changes in energy allocation. In a simulation study with the DEB model, we compared the effects of three hypothetical toxicants in different feeding situations. The initial food limitation when fed with lettuce always intensified the effect of the toxicants. When fed with fish flakes, the predicted effect of the toxicants was less pronounced. From this study, we conclude that (i) the proposed test conditions for L. stagnalis are not optimal, and require further investigation, (ii) fish flakes are a better food source for juvenile pond snails than lettuce, (iii) analyzing data with a mechanistic modeling approach such as DEB allows identifying deviations from constant conditions, (iv) being unaware of food limitation in the laboratory can lead to an overestimation of toxicity in ecotoxicological tests. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10646-012-0973-5) contains supplementary material, which is available to authorized users