@article{50b0ad588619463190bf1fd643fb08ed,
title = "Tightly linked antagonistic-effect loci underlie polygenic phenotypic variation in C. elegans",
abstract = "Recent work has provided strong empirical support for the classic polygenic model for trait variation. Population-based findings suggest that most regions of genome harbor variation affecting most traits. Here, we use the approach of experimental genetics to show that, indeed, most genomic regions carry variants with detectable effects on growth and reproduction in Caenorhabditis elegans populations sensitized by nickel stress. Nine of 15 adjacent intervals on the X chromosome, each encompassing ∼0.001 of the genome, have significant effects when tested individually in near-isogenic lines (NILs). These intervals have effects that are similar in magnitude to those of genome-wide significant loci that we mapped in a panel of recombinant inbred advanced intercross lines (RIAILs). If NIL-like effects were randomly distributed across the genome, the RIAILs would exhibit phenotypic variance that far exceeds the observed variance. However, the NIL intervals are arranged in a pattern that significantly reduces phenotypic variance relative to a random arrangement; adjacent intervals antagonize one another, cancelling each other's effects. Contrary to the expectation of small additive effects, our findings point to large-effect variants whose effects are masked by epistasis or linkage disequilibrium between alleles of opposing effect.",
keywords = "Complex traits, genetic architecture, linkage",
author = "Bernstein, {Max R.} and Stefan Zdraljevic and Andersen, {Erik C.} and Rockman, {Matthew V.}",
note = "Funding Information: MB and MVR conceived and designed the study with input from SZ and ECA; MB and SZ performed experiments; MB, SZ, ECA, and MVR analyzed the data; MB and MVR drafted the manuscript; and all authors contributed to the final version. This work was supported by NIH R01GM089972 and R01GM121828 (MVR), and funding to ECA from an NIH subcontract (GM107227), the Chicago Biomedical Consortium with support from the Searle Funds at the Chicago Community Trust, and an American Cancer Society Research Scholar Grant (127313- RSG-15-135-01-DD). Support for SZ came from the NIH Cell and Molecular Basis of Disease training grant (T32GM008061). We thank J. Bloom, I. Ruvinsky, T. Turner, and three reviewers for helpful comments. The authors declare no conflicts of interest. The data and code to reproduce the analyses in the paper are included as the Supporting Information Material. Funding Information: This work was supported by NIH R01GM089972 and R01GM121828 (MVR), and funding to ECA from an NIH subcontract (GM107227), the Chicago Biomedical Consortium with support from the Searle Funds at the Chicago Community Trust, and an American Cancer Society Research Scholar Grant (127313‐ RSG‐15‐135‐01‐DD). Support for SZ came from the NIH Cell and Molecular Basis of Disease training grant (T32GM008061). We thank J. Bloom, I. Ruvinsky, T. Turner, and three reviewers for helpful comments. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2019 The Author(s). Evolution Letters published by Wiley Periodicals, Inc. on behalf of Society for the Study of Evolution (SSE) and European Society for Evolutionary Biology (ESEB).",
year = "2019",
month = oct,
doi = "10.1002/evl3.139",
language = "English (US)",
volume = "3",
pages = "462--473",
journal = "Evolution Letters",
issn = "2056-3744",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",
}