Drosophila, the golden bug, emerges as a tool for human genetics. Nat Rev Genet

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


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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    • "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.
    Proteomics 07/2015; DOI:10.1002/pmic.201500092 · 3.81 Impact Factor
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    • "We refer the readers to several review articles that describe additional examples (Rubin and Lewis 2000; Bier 2005; Spradling et al. 2006; Arias 2008; Bellen et al. 2010). Genetics and epigenetics It is difficult to overstate the contribution of discoveries grounded in Drosophila genetics in the first part of the 20th century initiated by Thomas Hunt Morgan and his trainees. "
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    ABSTRACT: Many scientists complain that the current funding situation is dire. Indeed, there has been an overall decline in support in funding for research from the National Institutes of Health and the National Science Foundation. Within the Drosophila field, some of us question how long this funding crunch will last as it demotivates principal investigators and perhaps more importantly affects the longterm career choice of many young scientists. Yet numerous very interesting biological processes and avenues remain to be investigated in Drosophila, and probing questions can be answered fast and efficiently in flies to reveal new biological phenomena. Moreover, Drosophila is an excellent model organism for studies that have translational impact for genetic disease and for other medical implications such as vector-borne illnesses. We would like to promote a better collaboration between Drosophila geneticists/biologists and human geneticists/bioinformaticians/clinicians, as it would benefit both fields and significantly impact the research on human diseases. Copyright © 2015, The Genetics Society of America.
    Genetics 01/2015; 199(3). DOI:10.1534/genetics.114.171785 · 5.96 Impact Factor
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    • "We also screened for alterations in the color of bristles and cuticle to permit identification of genes involved in dopamine synthesis, secretion, metabolism, or melanization (Yamamoto and Seto, 2014) (Figure S2D). In addition, we selected mutations that affect wing morphogenesis to isolate genes that regulate core signaling pathways, including Notch, Wnt, Hedgehog, and BMP/TGF-b (Bier, 2005) (Figures S2E– S2J). Indeed, these pathways have been implicated in synaptic plasticity and neuronal maintenance in both fly and vertebrate nervous systems. "
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    ABSTRACT: Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human data sets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health.
    Cell 09/2014; 159(1):200–214. DOI:10.1016/j.cell.2014.09.002 · 32.24 Impact Factor
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