Article

Bier, E. Drosophila, the golden bug, emerges as a tool in human genetics. Nature Rev. Genet. 6, 9-23

Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92039, USA.
Nature Reviews Genetics (Impact Factor: 36.98). 02/2005; 6(1):9-23. DOI: 10.1038/nrg1503
Source: PubMed

ABSTRACT

Drosophila melanogaster is emerging as one of the most effective tools for analyzing the function of human disease genes, including those responsible for developmental and neurological disorders, cancer, cardiovascular disease, metabolic and storage diseases, and genes required for the function of the visual, auditory and immune systems. Flies have several experimental advantages, including their rapid life cycle and the large numbers of individuals that can be generated, which make them ideal for sophisticated genetic screens, and in future should aid the analysis of complex multigenic disorders. The general principles by which D. melanogaster can be used to understand human disease, together with several specific examples, are considered in this review.

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    • "Data obtained from proteome analysis are equally important, since 60% of the 289 genes implicated in human diseases have homologs in Drosophila, while 75% have similar protein sequences in both organisms [9], thus revealing a high conservation between biochemical routes and regulatory functions in both species [10]. Given these similarities, Drosophila is considered a suitable model for the study of genotoxicity and its molecular mechanisms [11] "
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    ABSTRACT: Biological, and particularly antimicrobial, activities have been demonstrated for the essential oil of propolis samples worlwide, yet their mutagenic effects remain unknown. To correlate antimicrobial effects with mutagenic risks, the present study evaluated the antifungal and antibacterial activities of the essential oil obtained from brown propolis collected from the Cerrado biome in Midwest Brazil (EOP), testing it against nine pathogenic microorganisms. Evaluation of mutagenic potential was based on the somatic mutation and recombination test (SMART) performed on wing cells of standard (ST) and high-bioactivation (HB) crosses of Drosophila melanogaster. EOP was extracted by hydrodistillation, and sesquiterpenes were characterized by GC–MS as its major constituents. The crude oil proved active against Cryptococcus neoformans and Enterococcus faecalis, as did two of its major constituents, spathulenol and (E)-nerolidol – the latter being also active against Staphylococcus aureus – isolated using chromatographic procedures. No significant increase in the number of somatic mutations was observed in the offspring of ST or HB crosses – the latter exhibiting enhanced levels of metabolizing enzymes of the cytochrome P450 type – treated with 0.05%, 0.1%, and 0.2% EOP. These findings revealed no mutagenic activity of EOP, even when tested against the HB strain, and demonstrated that its antimicrobial activities are not associated with DNA damage induction (investigated with SMART), suggesting the potential of EOP as a natural preservative.
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    • "Complex visual phenotypes have subsequently been deployed to systematically identify genes involved in embryonic development (NüVolhard and Wieschaus, 1980) and to identify genes that enhance or suppress known mutations (e.g.,Karim et al., 1996) (Figure 1A). Genetic screens for visual phenotypes have been among the most successful genetic approaches used over the past few decades (Bier, 2005;St Johnston, 2002). In particular, the richness and complexity of visual phenotypes are important factors in determining the specificity of a gene's effect, and visual phenotypes are an important tool for classifying genes by similarity into pathways and processes. "
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    ABSTRACT: Image-based screening is used to measure a variety of phenotypes in cells and whole organisms. Combined with perturbations such as RNA interference, small molecules, and mutations, such screens are a powerful method for gaining systematic insights into biological processes. Screens have been applied to study diverse processes, such as protein-localization changes, cancer cell vulnerabilities, and complex organismal phenotypes. Recently, advances in imaging and image-analysis methodologies have accelerated large-scale perturbation screens. Here, we describe the state of the art for image-based screening experiments and delineate experimental approaches and image-analysis approaches as well as discussing challenges and future directions, including leveraging CRISPR/Cas9-mediated genome engineering.
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    • "A complete genome of D. melanogaster has been determined [2] and protein-coding regions are well-annotated. Surprisingly, the human and the drosophila genome are apparently interrelated: The majority of human genes have counterparts in the fly genome and almost 75% of all known human disorder-related genes have fly homologues [3]. This, together with amenability in the genetic manipulations has made Drosophila a powerful, simple model to understand human biology, and molecular and cellular mechanisms of human diseases. "
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    ABSTRACT: Membrane proteins play key roles in several fundamental biological processes such as cell signalling, energy metabolism and transport. Despite the significance, these still remain an under-represented group in proteomics datasets. Herein, a bottom-up approach to analyse an enriched membrane fraction from Drosophila melanogaster heads using multidimensional liquid chromatography (LC) coupled with tandem-mass spectrometry (MS/MS) that relies on complete solubilisation and digestion of proteins, is reported. An enriched membrane fraction was prepared using equilibrium density centrifugation on a discontinuous sucrose gradient, followed by solubilisation using the filter-aided sample preparation (FASP), tryptic and sequential chymotryptic digestion of proteins. Peptides were separated by reversed-phase (RP) LC at high pH in the first dimension and acidic RP-LC in the second dimension coupled directly to an Orbitrap Velos Pro mass spectrometer. A total number of 4812 proteins from 114865 redundant and 38179 distinct peptides corresponding to 4559 genes were identified in the enriched membrane fraction from fly heads. These included brain receptors, transporters and channels that are most important elements as drug targets or are linked to disease. Data are available via ProteomeXchange with identifier PXD001712. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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