Genes2013, 4(4), 646-665; doi:10.3390/genes4040646 - published online 25 November 2013 Show/Hide Abstract
Abstract: RNA interference (RNAi) is a technique widely used for gene silencing in organisms and cultured cells, and depends on sequence homology between double-stranded RNA (dsRNA) and target mRNA molecules. Numerous cell-based genome-wide screens have successfully identified novel genes involved in various biological processes, including signal transduction, cell viability/death, and cell morphology. However, cell-based screens cannot address cellular processes such as development, behavior, and immunity. Drosophila and Caenorhabditis elegans are two model organisms whose whole bodies and individual body parts have been subjected to RNAi-based genome-wide screening. Moreover, Drosophila RNAi allows the manipulation of gene function in a spatiotemporal manner when it is implemented using the Gal4/UAS system. Using this inducible RNAi technique, various large-scale screens have been performed in Drosophila, demonstrating that the method is straightforward and valuable. However, accumulated results reveal that the results of RNAi-based screens have relatively high levels of error, such as false positives and negatives. Here, we review in vivo RNAi screens in Drosophila and the methods that could be used to remove ambiguity from screening results.
Genes2013, 4(4), 620-645; doi:10.3390/genes4040620 - published online 7 November 2013 Show/Hide Abstract
Abstract: Gene silencing through RNA interference (RNAi) is gaining momentum for crustaceans, both in basic research and for commercial development. RNAi has proven instrumental in a growing number of crustacean species, revealing the functionality of novel crustacean genes essential among others to development, growth, metabolism and reproduction. Extensive studies have also been done on silencing of viral transcripts in crustaceans, contributing to the understanding of the defense mechanisms of crustaceans and strategies employed by viruses to overcome these. The first practical use of gene silencing in aquaculture industry has been recently achieved, through manipulation of a crustacean insulin-like androgenic gland hormone. This review summarizes the advancements in the use of RNAi in crustaceans, and assesses the advantages of this method, as well as the current hurdles that hinder its large-scale practice.
Genes2013, 4(4), 596-619; doi:10.3390/genes4040596 - published online 5 November 2013 Show/Hide Abstract
Abstract: Up to 40% of patients with type 1 and type 2 diabetes will develop diabetic nephropathy (DN), resulting in chronic kidney disease and potential organ failure. There is evidence for a heritable genetic susceptibility to DN, but despite intensive research efforts the causative genes remain elusive. Recently, genome-wide association studies have discovered several novel genetic variants associated with DN. The identification of such variants may potentially allow for early identification of at risk patients. Here we review the current understanding of the key molecular mechanisms and genetic architecture of DN, and discuss the merits of employing an integrative approach to incorporate datasets from multiple sources (genetics, transcriptomics, epigenetic, proteomic) in order to fully elucidate the genetic elements contributing to this serious complication of diabetes.
Genes2013, 4(4), 583-595; doi:10.3390/genes4040583 - published online 25 October 2013 Show/Hide Abstract
Abstract: Insoluble nickel compounds are well-established human carcinogens. Occupational exposure to these compounds leads to increased incidence of lung and nasal cancer in nickel refinery workers. Apart from its weak mutagenic activity and hypoxia mimicking effect there is mounting experimental evidence indicating that epigenetic alteration plays an important role in nickel-induced carcinogenesis. Multiple epigenetic mechanisms have been identified to mediate nickel-induced gene silencing. Nickel ion is able to induce heterochromatinization by binding to DNA-histone complexes and initiating chromatin condensation. The enzymes required for establishing or removing epigenetic marks can be targeted by nickel, leading to altered DNA methylation and histone modification landscapes. The current review will focus on the epigenetic changes that contribute to nickel-induced gene silencing.
Genes2013, 4(4), 573-582; doi:10.3390/genes4040573 - published online 24 October 2013 Show/Hide Abstract
Abstract: Retroviruses, a form of mobile genetic elements, have important roles in disease and primate evolution. Exogenous retroviruses, such as human immunodeficiency virus (HIV), have significant pathological implications that have created a massive public health challenge in recent years. Endogenous retroviruses (ERVs), which are the primary focus of this review, can also be pathogenic, as well as being beneficial to a host in some cases. Furthermore, retroviruses may have played a key role in primate evolution that resulted in the incorporation of these elements into the human genome. Retroviruses are mobile genetic elements that have important roles in disease and primate evolution. We will further discuss the pathogenic potential of retroviruses, including their role in cancer biology, and will briefly summarize their evolutionary implications.
Genes2013, 4(4), 556-572; doi:10.3390/genes4040556 - published online 14 October 2013 Show/Hide Abstract
Abstract: The impact of bacterial diseases on public health has become enormous, and is partly due to the increasing trend of antibiotic resistance displayed by bacterial pathogens. Sequencing of bacterial genomes has significantly improved our understanding about the biology of many bacterial pathogens as well as identification of novel antibiotic targets. Since the advent of genome sequencing two decades ago, about 1,800 bacterial genomes have been fully sequenced and these include important aetiological agents such as Streptococcus pneumoniae, Mycobacterium tuberculosis, Escherichia coli O157:H7, Vibrio cholerae, Clostridium difficile and Staphylococcus aureus. Very recently, there has been an explosion of bacterial genome data and is due to the development of next generation sequencing technologies, which are evolving so rapidly. Indeed, the field of microbial genomics is advancing at a very fast rate and it is difficult for researchers to be abreast with the new developments. This highlights the need for regular updates in microbial genomics through comprehensive reviews. This review paper seeks to provide an update on bacterial genome sequencing generally, and to analyze insights gained from sequencing in two areas, including bacterial pathogenesis and the development of antibiotics.