Advances in Genetics最新文献

The prevalence of non-communicable diseases has been on an upward trajectory for some time and this puts an enormous burden on the healthcare expenditure. Lifestyle modifications including dietary interventions hold an immense promise to manage and prevent these diseases. Recent advances in genomic research provide evidence that focussing these efforts on individual variations in abilities to metabolize nutrients (nutrigenetics) and exploring the role of dietary compounds on gene expression (nutrigenomics and nutri-epigenomics) can lead to more meaningful personalized dietary strategies to promote optimal health. This chapter aims to provide examples on these gene-diet interactions at multiple levels to support the need of embedding targeted dietary interventions as a way forward to prevent, avoid and manage diseases.

Natural or synthetic compounds that interfere with the bioavailability of nutrients are called antinutrients. Phytic acid (PA) is one of the major antinutrients present in the grains and acts as a chelator of micronutrients. The presence of six reactive phosphate groups in PA hinders the absorption of micronutrients in the gut of non-ruminants. Consumption of PA-rich diet leads to deficiency of minerals such as iron and zinc among human population. On the contrary, PA is a natural antioxidant, and PA-derived molecules function in various signal transduction pathways. Therefore, optimal concentration of PA needs to be maintained in plants to avoid adverse pleiotropic effects, as well as to ensure micronutrient bioavailability in the diets. Given this, the chapter enumerates the structure, biosynthesis, and accumulation of PA in food grains followed by their roles in growth, development, and stress responses. Further, the chapter elaborates on the antinutritional properties of PA and explains the conventional breeding and transgene-based approaches deployed to develop low-PA varieties. Studies have shown that conventional breeding methods could develop low-PA lines; however, the pleiotropic effects of these methods viz. reduced yield, embryo abnormalities, and poor seed quality hinder the use of breeding strategies. Overexpression of phytase in the endosperm and RNAi-mediated silencing of genes involved in myo-inositol biosynthesis overcome these constraints. Next-generation genome editing approaches, including CRISPR-Cas9 enable the manipulation of more than one gene involved in PA biosynthesis pathway through multiplex editing, and scope exists to deploy such tools in developing varieties with optimal PA levels.

Preventive population genomics offers the prospect of population stratification for targeting screening and prevention and tailoring care to those at greatest risk. Within cancer, this approach is now within reach, given our expanding knowledge of its heritable components, improved ability to predict risk, and increasing availability of effective preventive strategies. Advances in technology and bioinformatics has made population-testing technically feasible. The BRCA model provides 30 years of insight and experience of how to conceive of and construct care and serves as an initial model for preventive population genomics. Population-based BRCA-testing in the Jewish population is feasible, acceptable, reduces anxiety, does not detrimentally affect psychological well-being or quality of life, is cost-effective and is now beginning to be implemented. Population-based BRCA-testing and multigene panel testing in the wider general population is cost-effective for numerous health systems and can save thousands more lives than the current clinical strategy. There is huge potential for using both genetic and non-genetic information in complex risk prediction algorithms to stratify populations for risk adapted screening and prevention. While numerous strides have been made in the last decade several issues need resolving for population genomics to fulfil its promise and potential for maximizing precision prevention. Healthcare systems need to overcome significant challenges associated with developing delivery pathways, infrastructure expansion including laboratory services, clinical workforce training, scaling of management pathways for screening and prevention. Large-scale real world population studies are needed to evaluate context specific population-testing implementation models for cancer risk prediction, screening and prevention.

Scientists working in natural products chemistry have been enticed by the current advancements being made in the discovery of novel "magic bullets" from microbes homed to all conceivable environments. Even though researchers continue to face challenges funneling the novel bioactive compounds in the global therapeutic industries, it seems most likely that the discovery of some "hit molecules" with significant biomedical applications is not that far. We applaud novel natural products for their ability to combat the spread of superbugs and aid in the prevention of currently observed antibiotic resistance. This in-depth investigation covers a wide range of microbiomes with a proclivity for synthesizing novel compounds to combat the spread of superbugs. Furthermore, we use this opportunity to explore various groups of secondary metabolites and their biosynthetic pathways in various microbiota found in mammals, insects, and humans. This systematic study, when taken as a whole, offers detail understanding on the biomedical fate of various groups of compounds originated from diverse microbiomes. For gathering all information that has been uncovered and released so far, we have also presented the huge diversity of microbes that are associated with humans and their metabolic products. To conclude, this concrete review suggests novel ideas that will prove immensely helpful in reducing the danger posed by superbugs while also improving the efficacy of antibiotics.

While asthma has a strong genetic component, our current ability to systematically understand and predict asthma risk remains low, despite over a hundred genetic associations. The reasons for this unfilled gap range from technical limitations of current approaches to fundamental deficiencies in the way we understand asthma. These are discussed in the context of genomic advances.

Genomic characterization of lung cancer has not only improved our understanding of disease biology and carcinogenesis but also revealed several therapeutic opportunities. Targeting tumor dependencies on specific genomic alterations (oncogene addiction) has accelerated the therapeutic developments and significantly improved the outcomes even in advanced stage of disease. Identification of genomic alterations predicting response to specific targeted treatment is the key to success for this "personalized treatment" approach. Availability of multiple choices of therapeutic options for specific genomic alterations highlight the importance of optimum sequencing of drugs. Multiplex gene testing has become mandatory in view of constantly increasing number of therapeutic targets and effective treatment options. Influence of genomic characteristics on response to immunotherapy further makes comprehensive genomic profiling necessary before therapeutic decision making. A comprehensive elucidation of resistance mechanisms and directed treatments have made the continuum of care possible and transformed this deadly disease into a chronic condition. Liquid biopsy-based approach has made the dynamic monitoring of disease possible and enabled treatment optimizations accordingly. Current lung cancer management is the perfect example of "precision-medicine" in clinical oncology.

Human migration and community specific cultural practices have contributed to founder events and enrichment of the variants associated with genetic diseases. While many founder events in isolated populations have remained uncharacterized, the application of genomics in clinical settings as well as for population scale studies in the recent years have provided an unprecedented push towards identification of founder variants associated with human health and disease. The discovery and characterization of founder variants could have far reaching implications not only in understanding the history or genealogy of the disease, but also in implementing evidence based policies and genetic testing frameworks. This further enables precise diagnosis and prevention in an attempt towards precision medicine. This review provides an overview of founder variants along with methods and resources cataloging them. We have also discussed the public health implications and examples of prevalent disease associated founder variants in specific populations.

Secondary metabolites synthesized by fungi have become a precious source of inspiration for the design of novel drugs. Indeed, fungi are prolific producers of fascinating, diverse, structurally complex, and low-molecular-mass natural products with high therapeutic leads, such as novel antimicrobial compounds, anticancer compounds, immunosuppressive agents, among others. Given that these microorganisms possess the extraordinary capacity to secrete diverse chemical scaffolds, they have been highly exploited by the giant pharma companies to generate small molecules. This has been made possible because the isolation of metabolites from fungal natural sources is feasible and surpasses the organic synthesis of compounds, which otherwise remains a significant bottleneck in the drug discovery process. Here in this comprehensive review, we have discussed recent studies on different fungi (pathogenic, non-pathogenic, commensal, and endophytic/symbiotic) from different habitats (terrestrial and marines), the specialized metabolites they biosynthesize, and the drugs derived from these specialized metabolites. Moreover, we have unveiled the logic behind the biosynthesis of vital chemical scaffolds, such as NRPS, PKS, PKS-NRPS hybrid, RiPPS, terpenoids, indole alkaloids, and their genetic mechanisms. Besides, we have provided a glimpse of the concept behind mycotoxins, virulence factor, and host immune response based on fungal infections.