Advances in Genetics

Several species of the Agrobacterium genus represent unique bacterial pathogens able to genetically transform plants, by transferring and integrating a segment of their own DNA (T-DNA, transferred DNA) in their host genome. Whereas in nature this process results in uncontrolled growth of the infected plant cells (tumors), this capability of Agrobacterium has been widely used as a crucial tool to generate transgenic plants, for research and biotechnology. The virulence of Agrobacterium relies on a series of virulence genes, mostly encoded on a large plasmid (Ti-plasmid, tumor inducing plasmid), involved in the different steps of the DNA transfer to the host cell genome: activation of bacterial virulence, synthesis and export of the T-DNA and its associated proteins, intracellular trafficking of the T-DNA and effector proteins in the host cell, and integration of the T-DNA in the host genomic DNA...

Acid-resistance in gastric pathogen Helicobacter pylori requires the coordination of four essential processes to regulate urease activity. Firstly, urease expression above a base level needs to be finely tuned at different ambient pH. Secondly, as nickel is needed to activate urease, nickel homeostasis needs to be maintained by proteins that import and export nickel ions, and sequester, store and release nickel when needed. Thirdly, urease accessary proteins that activate urease activity by nickel insertion need to be expressed...

Bacteria face a challenge when DNA enters their cells by transformation, mating, or phage infection. Should they treat this DNA as an invasive foreigner and destroy it, or consider it one of their own and potentially benefit from incorporating new genes or alleles to gain useful functions? It is frequently stated that the short nucleotide sequence Chi (5' GCTGGTGG 3'), a hotspot of homologous genetic recombination recognized by Escherichia coli's RecBCD helicase-nuclease, allows E. coli to distinguish its DNA (self) from any other DNA (non-self) and to destroy non-self DNA, and that Chi is "over-represented" in the E...

No abstract text is available yet for this article.

In this review, we summarize the current challenges faced by cancer researchers and motivate the use of novel genomics solutions. We follow this up with a comprehensive overview of three recent genomics technologies: liquid biopsy, single-cell RNA sequencing and spatial transcriptomics. We discuss a few representative protocols/assays for each technology along with their strengths, weaknesses, optimal use-cases, and their current stage of clinical deployment by summarizing trial data. We focus on how these technologies help us develop a better understanding of cancer as a rapidly evolving heterogeneous genetic disease that modulates its immediate microenvironment leading to systemic macro-level changes in the patient body...

There has been a paradigm shift in the management of cancer, with the immense progress in cancer genomics. More and more targeted therapies are becoming available by the day and personalized medicine is becoming popular with specific drugs being designed for selected subgroups of patients. One such new class of targeted drugs in the armamentarium is Poly ADP Ribose Polymerase (PARP) inhibitors (PARPi), which inhibit the enzyme PARP, thus interfering with DNA repair. This strategy utilizes a pre-existing genomic lesion in tumors with homologous recombination repair defects (including BRCA mutations), weakening tumor cells further by blocking the alternate pathway of DNA repair...

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...

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...

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...

Prostate cancer heritability is attributed to a combination of rare, moderate to highly penetrant genetic variants as well as commonly occurring variants conferring modest risks [single nucleotide polymorphisms (SNPs)]. Some of the former type of variants (e.g., BRCA2 mutations) predispose particularly to aggressive prostate cancer and confer poorer prognoses compared to men who do not carry mutations. Molecularly targeted treatments such as PARP inhibitors have improved outcomes in men carrying somatic and/or germline DNA repair gene mutations...

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...

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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...

Developmental programs are under strict genetic control that favors robustness of the process. In order to guarantee the same outcome in different environmental situations, development is modulated by input pathways, which inform about external conditions. In the nematode Caenorhabditis elegans, the process of postembryonic development involves a series of stereotypic cell divisions, the progression of which is controlled by the nutritional status of the animal. C. elegans can arrest development at different larval stages, leading to cell arrest of the relevant divisions of the stage...

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...

Circadian rhythm disturbances are frequently described in psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia. Growing evidence suggests a biological connection between mental health and circadian rhythmicity, including the circadian influence on brain function and mood and the requirement for circadian entrainment by external factors, which is often impaired in mental illness. Mental (as well as physical) health is also adversely affected by circadian misalignment. The marked interindividual differences in this combined susceptibility, in addition to the phenotypic spectrum in traits related both to circadian rhythms and mental health, suggested the possibility of a shared genetic background and that circadian clock genes may also be candidate genes for psychiatric disorders...

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...

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.

No abstract text is available yet for this article.

No abstract text is available yet for this article.