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Published on: July 26, 2017
Quantitative trait loci controlling halothane sensitivity in Caenorhabditis elegans
B van Swinderen1, D R Shook, R H Ebert
1Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Summary
Genetic analysis reveals significant natural variation in volatile anesthetic (VA) sensitivity in C. elegans. A major genetic locus on chromosome V explains over 40% of this variation in response to halothane.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Volatile anesthetics (VA) disrupt nervous system function, but the genetic basis of sensitivity variation is poorly understood.
- Previous mutagenesis efforts have yielded limited success in identifying resistant strains.
- A quantitative genetic approach is needed to explore natural variation in VA sensitivity.
Purpose of the Study:
- To investigate the natural variation in sensitivity to the volatile anesthetic halothane in Caenorhabditis elegans.
- To identify genetic loci influencing halothane sensitivity in behavior.
- To determine if identified loci affect basal behavior or anesthetic metabolism.
Main Methods:
- Utilized recombinant-inbred strains of C. elegans derived from distinct lineages.
- Assessed halothane sensitivity (EC50) for coordinated movement and male mating behavior.
- Employed quantitative trait loci (QTL) mapping to identify genetic determinants.
Main Results:
- Demonstrated significant heritability and wide variation (13- and 4-fold ranges) in halothane sensitivity for movement and mating.
- Identified a major locus on chromosome V explaining >40% of phenotypic variance for both traits.
- Discovered five weaker, interacting loci contributing to the remaining variance.
Conclusions:
- Natural genetic variation significantly impacts volatile anesthetic sensitivity in C. elegans.
- A major locus on chromosome V and several minor loci control halothane sensitivity.
- Identified QTL likely represent direct targets or downstream effectors of halothane in the nervous system, not basal behavior or metabolism differences.
