ALBERT

Description: : Although the 1000 Genomes haplotypes are the most commonly used reference panel for imputation, medical sequencing projects are generating large alternate sets of sequenced samples. Imputation in African Americans using 3384 haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from 1000 Genomes Project, increased effective sample size by 8.3–11.4% for coding variants with minor allele frequency 〈1%. No loss of imputation quality was observed using a panel built from phenotypic extremes. We recommend using haplotypes from Exome Sequencing Project alone or concatenation of the two panels over quality score-based post-imputation selection or IMPUTE2’s two-panel combination. Contact: yunli@med.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: The study of genetic influences on drug response and efficacy (‘pharmacogenetics’) has existed for over 50 years. Yet, we still lack a complete picture of how genetic variation, both common and rare, affects each individual's responses to medications. Exome sequencing is a promising alternative method for pharmacogenetic discovery as it provides information on both common and rare variation in large numbers of individuals. Using exome data from 2203 AA and 4300 Caucasian individuals through the NHLBI Exome Sequencing Project, we conducted a survey of coding variation within 12 Cytochrome P450 ( CYP ) genes that are collectively responsible for catalyzing nearly 75% of all known Phase I drug oxidation reactions. In addition to identifying many polymorphisms with known pharmacogenetic effects, we discovered over 730 novel nonsynonymous alleles across the 12 CYP genes of interest. These alleles include many with diverse functional effects such as premature stop codons, aberrant splicesites and mutations at conserved active site residues. Our analysis considering both novel, predicted functional alleles as well as known, actionable CYP alleles reveals that rare, deleterious variation contributes markedly to the overall burden of pharmacogenetic alleles within the populations considered, and that the contribution of rare variation to this burden is over three times greater in AA individuals as compared with Caucasians. While most of these impactful alleles are individually rare, 7.6–11.7% of individuals interrogated in the study carry at least one newly described potentially deleterious alleles in a major drug-metabolizing CYP .

Description: Many coral reef fish species form predictable, transient spawning aggregations. Many aggregations are overfished, making them a target for spatial management. Here, we develop a per-recruit model to evaluate the performance of no-take marine reserves protecting transient spawning aggregations. The model consists of only 14 demographic and exploitation-related parameters. We applied the model to a protogynous grouper and a gonochoristic rabbitfish from Seychelles and tested six scenarios regarding the extent of protected areas, the level of fish spawning-site fidelity, and fishing effort redistribution post reserve implementation. Spawning aggregation reserves improve spawning-stock biomass-per-recruit and reduce the sex ratio bias in protogynous populations for all scenarios examined. However, these benefits are often small and vary among the different scenarios and as a function of sexual ontogeny. In all scenarios, increases in yield-per-recruit do not occur or are negligible. The long-term yield increases due to spawning aggregation reserves may still occur, but only if spawning-stock biomass recovery results in a recruitment subsidy. Given these limited benefits, the value of no-take reserves must be weighed against those of other management options, such as fishing effort reduction and seasonal fishery closures. The latter is particularly appropriate when spawning and non-spawning areas overlap in space.

Description: There is a global trend in the depletion of transient reef fish spawning aggregations ("FSAs"), making them a primary target for management with marine protected areas (MPAs). Here, we review the observed and likely effectiveness of FSA MPAs, discuss how future studies could fill knowledge gaps, and provide recommendations for MPA design based on species' life history and behaviour, enforcement potential, and management goals. Modelling studies indicate that FSA MPAs can increase spawning-stock biomass and normalize sex ratio in protogynous fish populations, unless fishing mortality remains high outside protected FSA sites and spawning times. In the field, observations of no change or continued decline in spawning biomass are more common than population recovery. When empirical studies suggest that FSA MPAs may not benefit fish productivity or recovery, extenuating factors such as insufficient time since MPA creation, poor or lack of enforcement, inadequate design, and poorly defined management objectives are generally blamed rather than failure of the MPA concept. Results from both the empirical and modelling literature indicate that FSA MPAs may not improve exploitable biomass and fisheries yields; however, investigations are currently too limited to draw conclusions on this point. To implement effective FSA MPAs, additional modelling work, long-term monitoring programmes at FSA sites, and collections of fisheries-dependent data are required, with greater attention paid to the design and enforcement of area closures. We recommend a harmonized, adaptive approach that combines FSA MPA design with additional management measures to achieve explicitly stated objectives. Conservation objectives and, therefore, an overall reduction in mortality rates should be targeted first. Fisheries objectives build on conservation objectives, in that they require an overall reduction in mortality rates while maintaining sufficient access to exploitable biomass. Communication among researchers, regulatory agencies, park authorities, and fishers will be paramount for effective action, along with significant funds for implementation and enforcement.

Description: Data visualization is an essential component of genomic data analysis. However, the size and diversity of the data sets produced by today’s sequencing and array-based profiling methods present major challenges to visualization tools. The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies, with support for both array-based and next-generation sequencing data, and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources, its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end, IGV supports flexible loading of local and remote data sets, and is optimized to provide high-performance data visualization and exploration on standard desktop systems. IGV is freely available for download from http://www.broadinstitute.org/igv , under a GNU LGPL open-source license.

Description: This article considers the unwieldy state of UK environmental legislation in 2013, after 25 years of innovation, ad hoc reform and political change. It shows that an appraisal of UK environmental legislation involves considering much more than primary legislation emanating from Westminster—secondary legislation, devolved legislative instruments, policy documents and administrative norms all serve to constitute and inform the legislative picture. Through this wide analytical lens, the article considers legal problems that characterise UK environmental legislation today, from undermining of the rule of law due to its inaccessible complexity, to occupying an awkward place in public law terms. A particular problem is the fragmentation of legislation, and the article examines the case for integrating environmental legislation in a way that does not undermine the flexibility and institutional expertise that more focused legislation allows. The article offers not only a method for analysing the current UK environmental legislative landscape, but suggests routes for reform that might now be considered.

Description: The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project.

Description: It is 14 years since the IMGT/HLA database was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Of these, 21 genes encode proteins of the immune system that are highly polymorphic. The naming of these HLA genes and alleles and their quality control is the responsibility of the World Health Organization Nomenclature Committee for Factors of the HLA System. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute, we are able to provide public access to these data through the website http://www.ebi.ac.uk/imgt/hla/ . Regular updates to the website ensure that new and confirmatory sequences are dispersed to the HLA community and the wider research and clinical communities. This article describes the latest updates and additional tools added to the IMGT/HLA project.

Description: microRNAs (miRNAs) are a key component of gene regulatory networks and have been implicated in the regulation of virtually every biological process found in multicellular eukaryotes. What makes them interesting from a phylogenetic perspective is the high conservation of primary sequence between taxa, their accrual in metazoan genomes through evolutionary time, and the rarity of secondary loss in most metazoan taxa. Despite these properties, the use of miRNAs as phylogenetic markers has not yet been discussed within a clear conceptual framework. Here we highlight five properties of miRNAs that underlie their utility in phylogenetics: 1) The processes of miRNA biogenesis enable the identification of novel miRNAs without prior knowledge of sequence; 2) The continuous addition of miRNA families to metazoan genomes through evolutionary time; 3) The low level of secondary gene loss in most metazoan taxa; 4) The low substitution rate in the mature miRNA sequence; and 5) The small probability of convergent evolution of two miRNAs. Phylogenetic analyses using both Bayesian and parsimony methods on a eumetazoan miRNA data set highlight the potential of miRNAs to become an invaluable new tool, especially when used as an additional line of evidence, to resolve previously intractable nodes within the tree of life.