Drosophila as a Genetic Model System for Understanding Human Biology and Disease

2001 ◽  
pp. 30-49
Keyword(s):  
Genetic Model ◽  
Model System ◽  
Human Biology

scholarly journals The utility of a closed breeding colony of Peromyscus leucopus for dissecting complex traits

2021 ◽  
Author(s):  
Anthony D Long ◽  
Alan Barbour ◽  
Phillip N Long ◽  
Vanessa J Cook ◽  
Arundhati Majumder
Keyword(s):  
Complex Traits ◽  
Genetic Model ◽  
Peromyscus Leucopus ◽  
False Positive Rate ◽  
Model System ◽  
Sequencing Data ◽  
Power Estimate ◽  
Genome Wide ◽  
Low Pass ◽  
Closed Colony

Although Peromyscus leucopus (deermouse) is not considered a genetic model system, its genus is well suited for addressing several questions of biologist interest, including the genetic bases of longevity, behavior, physiology, adaptation, and its ability to serve as a disease vector. Here we explore a diversity outbred approach for dissecting complex traits in Peromyscus leucopus, a non-traditional genetic model system. We take advantage of a closed colony of deer-mice founded from 38 individuals between 1982 and 1985 and subsequently maintained for 35+ years (~40-60 generations). From 405 low-pass (~1X) short-read sequenced deermice we accurately imputed genotypes at 17,751,882 SNPs. Conditional on observed genotypes for a subset of 297 individuals, simulations were conducted in which a QTL contributes 5% to a complex trait under three different genetic models. The power of either a haplotype- or marker-based statistical test was estimated to be 15-25% to detect the hidden QTL. Although modest, this power estimate is consistent with that of DO/HS mice and rat experiments for an experiment with ~300 individuals. This limitation in QTL detection is mostly associated with the stringent significance threshold required to hold the genome-wide false positive rate low, as in all cases we observe considerable linkage signal at the location of simulated QTL, suggesting a larger panel would exhibit greater power. For the subset of cases where a QTL was detected, localization ability appeared very desirable at ~1-2Mb. We finally carried out a GWAS on a demonstration trait, bleeding time. No tests exceeded the threshold for genome-wide significance, but one of four suggestive regions co-localizes with Von Willebrand factor. Our work suggests that complex traits can be dissected in founders-unknown P. leucopus colony mice in much the same manner as founders-known DO/HS mice and rats, with genotypes obtained from low pass sequencing data. Our results further suggest that the DO/HS approach can be powerfully extended to any system in which a founders-unknown closed colony has been maintained for several dozen generations.

scholarly journals The FDA-approved drugs ticlopidine, sertaconazole, and dexlansoprazole can cause morphological changes in C. elegans

2020 ◽  
Author(s):  
Kyle F Galford ◽  
Antony M Jose
Keyword(s):  
Proton Pump Inhibitor ◽  
Genetic Model ◽  
Morphological Changes ◽  
Model System ◽  
Model Organisms ◽  
Regulatory Agencies ◽  
C Elegans ◽  
Therapeutic Drugs ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractUrgent need for treatments limit studies of therapeutic drugs before approval by regulatory agencies. Analyses of drugs after approval can therefore improve our understanding of their mechanism of action and enable better therapies. We screened a library of 1443 Food and Drug Administration (FDA)-approved drugs using a simple assay in the nematode C. elegans and found three compounds that caused morphological changes. While the anticoagulant ticlopidine and the antifungal sertaconazole caused morphologically distinct pharyngeal defects upon acute exposure, the proton-pump inhibitor dexlansoprazole caused molting defects and required exposure during larval development. Such easily detectable defects in a powerful genetic model system advocate the continued exploration of current medicines using a variety of model organisms to better understand drugs already prescribed to millions of patients.

scholarly journals The fish watch: Zebrafish: a clock in every cell

2005 ◽  
Vol 27 (6) ◽  
pp. 23-26
Author(s):  
Amanda-Jayne F. Carr ◽  
David Whitmore
Keyword(s):  
Circadian Rhythms ◽  
Danio Rerio ◽  
Biological Process ◽  
Genetic Model ◽  
Model System ◽  
Biological Processes ◽  
Powerful Method ◽  
Dark Cycle ◽  
Environmental Light ◽  
The One

The environmental light–dark cycle is one of the most reliable rhythmic signals, and many organisms have evolved a circadian (circa diem, ‘about a day’) system to co-ordinate biological processes with this predictable environmental change. These rhythms are endogenous and persist even in constant conditions, the light–dark cycle serving to synchronize these rhythms precisely to 24 hours. Genetic approaches have proved invaluable in increasing our understanding of the circadian clock. The ability to isolate a mutant with a defect in a rhythmic process is a very powerful method, which depends on no prior assumptions about the biological process under investigation. Consequently, Drosophila and the mouse have become the most powerful genetic models to study circadian rhythms in animals. The one alternative vertebrate genetic model system to the mouse is the zebrafish (Danio rerio).

scholarly journals The Intestine of Drosophila melanogaster: An Emerging Versatile Model System to Study Intestinal Epithelial Homeostasis and Host-Microbial Interactions in Humans

2019 ◽  
Vol 7 (9) ◽  
pp. 336 ◽  
Author(s):  
Florence Capo ◽  
Alexa Wilson ◽  
Francesca Di Cara
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Model ◽  
Current Knowledge ◽  
Cell Lineage ◽  
Model Organism ◽  
Model System ◽  
Microbial Interactions ◽  
Stem Cell Lineage ◽  
Bowel Diseases

In all metazoans, the intestinal tract is an essential organ to integrate nutritional signaling, hormonal cues and immunometabolic networks. The dysregulation of intestinal epithelium functions can impact organism physiology and, in humans, leads to devastating and complex diseases, such as inflammatory bowel diseases, intestinal cancers, and obesity. Two decades ago, the discovery of an immune response in the intestine of the genetic model system, Drosophila melanogaster, sparked interest in using this model organism to dissect the mechanisms that govern gut (patho) physiology in humans. In 2007, the finding of the intestinal stem cell lineage, followed by the development of tools available for its manipulation in vivo, helped to elucidate the structural organization and functions of the fly intestine and its similarity with mammalian gastrointestinal systems. To date, studies of the Drosophila gut have already helped to shed light on a broad range of biological questions regarding stem cells and their niches, interorgan communication, immunity and immunometabolism, making the Drosophila a promising model organism for human enteric studies. This review summarizes our current knowledge of the structure and functions of the Drosophila melanogaster intestine, asserting its validity as an emerging model system to study gut physiology, regeneration, immune defenses and host-microbiota interactions.

Minor millets as model system to study C4 photosynthesis -A review

2015 ◽  
Vol 36 (4) ◽  
Author(s):  
P. Vivitha ◽  
D. Vijayalakshmi
Keyword(s):  
Distribution System ◽  
Genetic Model ◽  
Crop Improvement ◽  
Model System ◽  
Life Cycles ◽  
Model Systems ◽  
Subtype C ◽  
Model Species ◽  
Kranz Anatomy ◽  
Minor Millets

C<sub>4</sub> photosynthesis is the primary mode of carbon capture and drives productivity in several major food crops and bioenergy grasses. Gains in productivity associated with C<sub>4</sub> photosynthesis include improved water and nitrogen use efficiencies. Within grasses rice and brachypodium are used as model species. Since these two crops are using C<sub>3</sub> photosynthesis for their growth and development, it cannot be used as model for to study C<sub>4</sub> photosynthesis. In order to characterize the evolutionary innovations and to provide genomic insight into crop improvement for the many important crop species, a new genomic and genetic model species is required. Minor millets have small diploid genomes, shorter life cycles, self pollination and prolific seed production. Due to these characteristics it gains importance over major C<sub>4</sub> species which lack all of these traits. Within Minor millets, <italic>Setaria italica</italic> and <italic>Setaria viridis</italic> are used as model systems since these crops fulfils all the traits responsible to be a model species. Importantly, <italic>Setaria</italic> species uses NADP-Malic enzyme subtype C<sub>4</sub> photosynthetic system to fix carbon and therefore is a potential powerful model system for dissecting C<sub>4</sub> photosynthesis. C<sub>4</sub> grasses have a shorter distance between longitudinal veins in the leaves than C<sub>3</sub> grasses. The C<sub>4</sub> grasses have denser transverse and small longitudinal veins than the C<sub>3</sub> grasses. It indicates that C<sub>4</sub> grasses have a structurally superior photosynthate translocation and water distribution system by developing denser networks of small longitudinal and transverse veins. <italic>Setaria</italic> has high vein density and kranz anatomy that helps to concentrate CO<sub>2</sub> in the bundle sheath cells. This minimizes photorespiration thereby prevents the loss of energy.

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