ArticleG3 (Bethesda, Md.)2013
The genetic architecture of methotrexate toxicity is similar in Drosophila melanogaster and humans.
Article in G3 (Bethesda, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster.G3 (Bethesda, Md.) · 2024Article
- Genetic dissection of innate immune memory inFrontiers in immunology · 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
- Article
- 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
- FM0807 decelerates experimental arthritis progression by inhibiting inflammatory responses and joint destruction via modulating NF-κB and MAPK pathways.Bioscience reports · 2019Article
- Determinants of QTL Mapping Power in the Realized Collaborative Cross.G3 (Bethesda, Md.) · 2019Article
- The Sleep Inbred Panel, a Collection of InbredG3 (Bethesda, Md.) · 2018Article
- A Genomic Reference Panel forG3 (Bethesda, Md.) · 2018Article
- Natural diversity facilitates the discovery of conserved chemotherapeutic response mechanisms.Current opinion in genetics & development · 2017Review
- Loci Contributing to Boric Acid Toxicity in Two Reference Populations ofG3 (Bethesda, Md.) · 2017Article
- Influence of Quercetin in the Temporal Regulation of Redox Homeostasis in Drosophila melanogaster.Journal of insect science (Online) · 2017Article
- Genetic dissection of intraspecific variation in a male-specific sexual trait in Drosophila melanogaster.Heredity · 2016Article
- Article
- The impact of green tea polyphenols on development and reproduction inJournal of functional foods · 2016Article
- Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila.PLoS genetics · 2015Article
- The differential view of genotype-phenotype relationships.Frontiers in genetics · 2015Article
- Dissecting complex traits using the Drosophila Synthetic Population Resource.Trends in genetics : TIG · 2014Review
- Fine-mapping nicotine resistance loci in Drosophila using a multiparent advanced generation inter-cross population.Genetics · 2014Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The severity of the toxic side effects of chemotherapy varies among patients, and much of this variation is likely genetically based. Here, we use the model system Drosophila melanogaster to genetically dissect the toxicity of methotrexate (MTX), a drug used primarily to treat childhood acute lymphoblastic leukemia and rheumatoid arthritis. We use the Drosophila Synthetic Population Resource, a panel of recombinant inbred lines derived from a multiparent advanced intercross, and quantify MTX toxicity as a reduction in female fecundity. We identify three quantitative trait loci (QTL) affecting MTX toxicity; two colocalize with the fly orthologs of human genes believed to mediate MTX toxicity and one is a novel MTX toxicity gene with a human ortholog. A fourth suggestive QTL spans a centromere. Local single-marker association scans of candidate gene exons fail to implicate amino acid variants as the causative single-nucleotide polymorphisms, and we therefore hypothesize the causative variation is regulatory. In addition, the effects at our mapped QTL do not conform to a simple biallelic pattern, suggesting multiple causative factors underlie the QTL mapping results. Consistent with this observation, no single single-nucleotide polymorphism located in or near a candidate gene can explain the QTL mapping signal. Overall, our results validate D. melanogaster as a model for uncovering the genetic basis of chemotoxicity and suggest the genetic basis of MTX toxicity is due to a handful of genes each harboring multiple segregating regulatory factors.
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What OpenQuestion holds
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.