The genetics of nontuberculous mycobacterial infection

The molecular aetiology of familial susceptibility to disseminated mycobacterial disease, usually involving weakly pathogenic strains of mycobacteria, has now been elucidated in more than 30 families. Mutations have been identified in five genes in the interleukin-12-dependent interferon-gamma pathway, highlighting the importance of this pathway in human mycobacterial immunity. Knowledge derived from the study of these rare patients contributes to our understanding of the immune response to common mycobacterial pathogens such as Mycobacterium tuberculosis and Mycobacterium leprae, which remain major public health problems globally. This knowledge can be applied to the rational development of novel therapies and vaccines for these important mycobacterial diseases.     

Using genetics to inform re-introduction strategies for the Chequered Skipper butterfly (Carterocephalus palaemon, Pallas) in England

The Chequered Skipper butterfly (Carterocephalus palaemon) is extinct in England but extant in Scotland and Continental Europe. The possibility of re-introducing the species is under active consideration by conservation bodies, but ecological differences between Scottish and English populations raise the question of which populations should donate individuals, Continental European, or Scottish? We used mitochondrial DNA sequences (CO I, CO II and Cyt b) from potential donor populations to test the hypothesis that ecological differences could have arisen as a result of differing routes of post-glacial colonisation from separate refugia and subsequent isolation of UK populations. Shared haplotypes between populations in Belgium, Norway, Scotland and England provides no evidence to support the hypothesis that populations in Scotland result from an alternative post-glacial colonisation route. As the genetic evidence remains equivocal we suggest that choice of donor stock for a re-introduction to England should be made primarily on ecological grounds.     

植物病原物的群体遗传学

品种单一化、生产密集型和一年多茬的现代农业特点导致病原物呈现出进化速度加快、致病力增强及流行风险增大趋势。深入研究病原物群体遗传学对认识病害的流行、有效选育和使用抗性品种乃至控制病害具有重要意义。文章阐述了植物病原物群体遗传学的研究目标和内容、突变、基因迁移、基因重组、随机遗传漂变和自然选择5大遗传机制在植物病原物进化过程中的作用, 以及目前植物病原物群体遗传学研究的现状。     

植物病原物的群体遗传学

品种单一化、生产密集型和一年多茬的现代农业特点导致病原物呈现出进化速度加快、致病力增强及流行风险增大趋势。深入研究病原物群体遗传学对认识病害的流行、有效选育和使用抗性品种乃至控制病害具有重要意义。文章阐述了植物病原物群体遗传学的研究目标和内容、突变、基因迁移、基因重组、随机遗传漂变和自然选择5大遗传机制在植物病原物进化过程中的作用,以及目前植物病原物群体遗传学研究的现状。     

Receptor‐mediated recognition of mycobacterial pathogens

Mycobacteria are a genus of bacteria that range from the non‐pathogenic Mycobacterium smegmatis to Mycobacterium tuberculosis, the causative agent of tuberculosis in humans. Mycobacteria primarily infect host tissues through inhalation or ingestion. They are phagocytosed by host macrophages and dendritic cells. Here, conserved pathogen‐associated molecular patterns (PAMPs) on the surface of mycobacteria are recognized by phagocytic pattern recognition receptors (PRRs). Several families of PRRs have been shown to non‐opsonically recognize mycobacterial PAMPs, including membrane‐bound C‐type lectin receptors, membrane‐bound and cytosolic Toll‐like receptors and cytosolic NOD‐like receptors. Recently, a possible role for intracellular cytosolic PRRs in the recognition of mycobacterial pathogens has been proposed. Here, we discuss currentideas on receptor‐mediated recognition of mycobacterial pathogens by macrophages and dendritic cells.     

Coevolutionary genetics of plants and pathogens

Summary The genetic polymorphism maintained by host-pathogen coevolution is analysed in a multilocus model. The model assumes gene-for-gene interactions of the type commonly observed between host plants and their fungal pathogens. Unstable (epidemic) systems maintain more resistance genes, fewer virulence genes, and less overall genetic diversity than stable (endemic) diseases. The stability of the system depends primarily on demographic parameters, such as the pathogen's intrinsic rate of increase, rather than genetic parameters, such as the costs of resistance and virulence. At equilibrium the model predicts that the number of resistance alleles in each host plant follows a binomial distribution that depends on the cost to the pathogen for carrying virulence alleles. Similarly, the number of virulence alleles in each pathogen spore follows a binomial distribution that depends on one minus the cost to the host for carrying resistance alleles. Data from wild populations match the predicted binomial distributions.     

Using biogeographical history to inform conservation: the case of Preble's meadow jumping mouse

The last Pleistocene deglaciation shaped temperate and boreal communities in North America. Rapid northward expansion into high latitudes created distinctive spatial genetic patterns within species that include closely related groups of populations that are now widely spread across latitudes, while longitudinally adjacent populations, especially those near the southern periphery, often are distinctive due to long‐term disjunction. Across a spatial expanse that includes both recently colonized and long‐occupied regions, we analysed molecular variation in zapodid rodents to explore how past climate shifts influenced diversification in this group. By combining molecular analyses with species distribution modelling and tests of ecological interchangeability, we show that the lineage including the Preble's meadow jumping mouse (Zapus hudsonius preblei), a US federally listed taxon of conservation concern, is not restricted to the southern Rocky Mountains. Rather, populations along the Front Range are part of a single lineage that is ecologically indistinct and extends to the far north. Of the 21 lineages identified, this Northern lineage has the largest geographical range and low measures of intralineage genetic differentiation, consistent with recent northward expansion. Comprehensive sampling combined with coalescent‐based analyses and niche modelling leads to a radically different view of geographical structure within jumping mice and indicates the need to re‐evaluate their taxonomy and management. This analysis highlights a premise in conservation biology that biogeographical history should play a central role in establishing conservation priorities.     

Sharing the benefits of genetic resources: from biodiversity to human genetics

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.     

Human genetic susceptibility to tuberculosis and other mycobacterial diseases

The existence of a genetic component in mycobacterial disease susceptibility is no longer in doubt and the investigations now being conducted aim to determine which genes are involved, to what extent, and in which disease phenotype they are relevant. In certain rare instances of susceptibility to poorly pathogenic mycobacteria, the genetic component is clear. The approaches employed to elucidate common disease susceptibility include linkage studies, particularly genome-wide linkage analysis of both tuberculosis and leprosy, and association studies. A number of candidate genes have shown association with tuberculosis, and in many cases, on replication of the study, association has been confirmed in a disparate population, indicating the wider importance of the gene in the disease process. In other instances, associations appear to be particular to a population or a subtype of disease.     

TB tools to tell the tale-molecular genetic methods for mycobacterial research

In spite of the availability of drugs and a vaccine, tuberculosis--one of man's medical nemeses--remains a formidable public health problem, particularly in the developing world. The persistent nature of the tubercle bacillus, with one third of the world's population is estimated to be infected, combined with the emergence of multi drug-resistant strains and the exquisite susceptibility of HIV-positive individuals, has underscored the urgent need for in-depth study of the biology of Mycobacterium tuberculosis address the resurgence of TB. In aiming to understand the mechanisms by which mycobacteria react to their immediate environments, molecular genetic tools have been developed from naturally occurring genetic elements. These include protein expressing genes, and episomal and integrating elements, which have been derived mainly from prokaryotic but also from eukaryotic organisms. Molecular genetic tools that had been established as routine procedures in other prokaryotic genera were thus mimicked. Knowledge of the underlying mechanisms greatly expedited the harnessing of these elements for mycobacteriological research and has brought us to a point where these molecular genetic tools are now employed routinely in laboratories worldwide.     

Using watershed characteristics to inform cost-effective stream temperature monitoring

Aquatic Ecology - Water temperature is a key driver of aquatic processes. Monitoring stream water temperature is key to understanding current species distributions and future climate change impacts...     

Digital genetics: unravelling the genetic basis of evolution

Digital genetics, or the genetics of digital organisms, is a new field of research that has become possible as a result of the remarkable power of evolution experiments that use computers. Self-replicating strands of computer code that inhabit specially prepared computers can mutate, evolve and adapt to their environment. Digital organisms make it easy to conduct repeatable, controlled experiments, which have a perfect genetic 'fossil record'. This allows researchers to address fundamental questions about the genetic basis of the evolution of complexity, genome organization, robustness and evolvability, and to test the consequences of mutations, including their interaction and recombination, on the fate of populations and lineages.     

ASSIMILATOR: a new tool to inform selection of associated genetic variants for functional studies

MOTIVATION: Fine-mapping experiments from genome-wide association studies (GWAS) are underway for many complex diseases. These are likely to identify a number of putative causal variants, which cannot be separated further in terms of strength of genetic association due to linkage disequilibrium. The challenge will be selecting which variant to prioritize for subsequent expensive functional studies. A wealth of functional information generated from wet lab experiments now exists but cannot be easily interrogated by the user. Here, we describe a program designed to quickly assimilate this data called ASSIMILATOR and validate the method by interrogating two regions to show its effectiveness. AVAILABILITY: http://www.medicine.manchester.ac.uk/musculoskeletal/research/arc/genetics/bioinformatics/assimilator/.