ArticlePLoS genetics2015
Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
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- Using Drosophila to identify naturally occurring genetic modifiers of amyloid beta 42- and tau-induced toxicity.G3 (Bethesda, Md.) · 2023Article
- The genetic basis of variation in immune defense against Lysinibacillus fusiformis infection in Drosophila melanogaster.PLoS pathogens · 2023Article
- Discovery of malathion resistance QTL in Drosophila melanogaster using a bulked phenotyping approach.G3 (Bethesda, Md.) · 2022Article
- Powerful, efficient QTL mapping in Drosophila melanogaster using bulked phenotyping and pooled sequencing.Genetics · 2022Article
- A Population Genomic Assessment of Three Decades of Evolution in a Natural Drosophila Population.Molecular biology and evolution · 2022Article
- Trade-offs between cost of ingestion and rate of intake drive defensive toxin use.Biology letters · 2022Article
- Ecdysteroid kinase-like (EcKL) paralogs confer developmental tolerance to caffeine inCurrent research in insect science · 2022Article
- The molecular architecture of Drosophila melanogaster defense against Beauveria bassiana explored through evolve and resequence and quantitative trait locus mapping.G3 (Bethesda, Md.) · 2021Article
- Dissecting the Genetic Basis of Variation inGenes · 2020Article
- Genome-Wide Association Study in Two Cohorts from a Multi-generational Mouse Advanced Intercross Line Highlights the Difficulty of Replication Due to Study-Specific Heterogeneity.G3 (Bethesda, Md.) · 2020Article
- Phenotypic Responses to and Genetic Architecture of Sterility Following Exposure to Sub-Lethal Temperature During Development.Frontiers in genetics · 2020Article
- Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster.Genes, brain, and behavior · 2019Article
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- Determinants of QTL Mapping Power in the Realized Collaborative Cross.G3 (Bethesda, Md.) · 2019Article
- Dissection of Complex, Fitness-Related Traits in MultipleGenetics · 2019Article
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- Gene Regulatory Variation inGenetics · 2018Article
- The Sleep Inbred Panel, a Collection of InbredG3 (Bethesda, Md.) · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Natural populations exhibit a great deal of interindividual genetic variation in the response to toxins, exemplified by the variable clinical efficacy of pharmaceutical drugs in humans, and the evolution of pesticide resistant insects. Such variation can result from several phenomena, including variable metabolic detoxification of the xenobiotic, and differential sensitivity of the molecular target of the toxin. Our goal is to genetically dissect variation in the response to xenobiotics, and characterize naturally-segregating polymorphisms that modulate toxicity. Here, we use the Drosophila Synthetic Population Resource (DSPR), a multiparent advanced intercross panel of recombinant inbred lines, to identify QTL (Quantitative Trait Loci) underlying xenobiotic resistance, and employ caffeine as a model toxic compound. Phenotyping over 1,700 genotypes led to the identification of ten QTL, each explaining 4.5-14.4% of the broad-sense heritability for caffeine resistance. Four QTL harbor members of the cytochrome P450 family of detoxification enzymes, which represent strong a priori candidate genes. The case is especially strong for Cyp12d1, with multiple lines of evidence indicating the gene causally impacts caffeine resistance. Cyp12d1 is implicated by QTL mapped in both panels of DSPR RILs, is significantly upregulated in the presence of caffeine, and RNAi knockdown robustly decreases caffeine tolerance. Furthermore, copy number variation at Cyp12d1 is strongly associated with phenotype in the DSPR, with a trend in the same direction observed in the DGRP (Drosophila Genetic Reference Panel). No additional plausible causative polymorphisms were observed in a full genomewide association study in the DGRP, or in analyses restricted to QTL regions mapped in the DSPR. Just as in human populations, replicating modest-effect, naturally-segregating causative variants in an association study framework in flies will likely require very large sample sizes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.