From QTL to gene: C. elegans facilitates discoveries of the genetic mechanisms underlying natural variation

Evans, Kathryn; Wijk, Marijke H. van; McGrath, Patrick T.; Andersen, Erik C.; Sterken, M.G.

doi:10.1016/j.tig.2021.06.005

Cited by 57 publications

(71 citation statements)

References 172 publications

(337 reference statements)

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“…Previous work has used GWA mappings to identify QTL and subsequently identify quantitative trait variants (QTV) in C. elegans (Evans et al 2021b). In order to test whether NemaScan performs similarly in practice to cegwas2-nf, the previous mapping pipeline (https://github.com/AndersenLab/cegwas2-nf) that used the EMMA algorithm (Kang et al 2008) implemented by R/rrBLUP (Endelman 2011), we re-mapped five quantitative traits using both cegwas2-nf and NemaScan.…”

Section: Nemascan Recapitulates Previously Validated Genetic Associationsmentioning

confidence: 99%

Evaluating the power and limitations of genome-wide association mapping in C. elegans

Widmayer

Evans

Zdraljevic

et al. 2021

Preprint

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A central goal of evolutionary genetics in Caenorhabditis elegans is to understand the genetic basis of traits that contribute to adaptation and fitness. Genome-wide association (GWA) mappings scan the genome for individual genetic variants that are significantly correlated with phenotypic variation in a population, or quantitative trait loci (QTL). GWA mappings are a popular choice for quantitative genetic analyses because the QTL that are discovered segregate in natural populations. Despite numerous successful mapping experiments, the empirical performance of GWA mappings has not, to date, been formally evaluated for this species. We developed an open-source GWA mapping pipeline called NemaScan and used a simulation-based approach to provide benchmarks of mapping performance among wild C. elegans strains. Simulated trait heritability and complexity determined the spectrum of QTL detected by GWA mappings. Power to detect smaller-effect QTL increased with the number of strains sampled from the C. elegans Natural Diversity Resource (CeNDR). Population structure was a major driver of variation in GWA mapping performance, with populations shaped by recent selection exhibiting significantly lower false discovery rates than populations composed of more divergent strains. We also recapitulated previous GWA mappings of experimentally validated quantitative trait variants. Our simulation-based evaluation of GWA performance provides the community with critical context for pursuing quantitative genetic studies using CeNDR to elucidate the genetic basis of complex traits in C. elegans natural populations.

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Section: Nemascan Recapitulates Previously Validated Genetic Associationsmentioning

confidence: 99%

Evaluating the power and limitations of genome-wide association mapping in C. elegans

Widmayer

Evans

Zdraljevic

et al. 2021

Preprint

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“…The nematode Caenorhabditis elegans is a powerful model to study the genetic basis of natural variation in diverse quantitative traits [14][15][16] . Genome-wide gene expression variation in different developmental stages and various conditions at the whole-organism or cellular resolution have been discovered and thousands of eQTL have been identified in several studies over the past two decades 3,9,[17][18][19][20][21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Consequently, the observed variation in gene expression and their identified eQTL were limited to the differences among a small number of C. elegans strains and only revealed a tiny fraction of the natural diversity of gene expression and regulatory mechanisms in this species. The C. elegans Natural Diversity Resource (CeNDR) has a collection of 540 genetically distinct wild C. elegans strains 16, 24, 25 . Variation in diverse organism-level phenotypes has been observed among these wild strains, and many underlying QTL, quantitative trait genes (QTGs), and quantitative trait variants (QTVs) have been identified using GWA mappings 15, 16 .…”

Section: Introductionmentioning

confidence: 99%

“…The C. elegans Natural Diversity Resource (CeNDR) has a collection of 540 genetically distinct wild C. elegans strains 16, 24, 25 . Variation in diverse organism-level phenotypes has been observed among these wild strains, and many underlying QTL, quantitative trait genes (QTGs), and quantitative trait variants (QTVs) have been identified using GWA mappings 15, 16 . Therefore, a genome-wide analysis could improve our understanding of the role of gene regulation in shaping organism-level phenotypic diversity, adaptation, and evolution of C. elegans .…”

Section: Introductionmentioning

confidence: 99%

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An atlas of gene expression variation across the Caenorhabditis elegans species

Zhang

Roberto

Lee

et al. 2022

Preprint

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Phenotypic variation in diverse organism-level traits have been studied in Caenorhabditis elegans wild strains, but differences in gene expression and the underlying variation in regulatory mechanisms are largely unknown. Here, we use natural variation in gene expression to connect genetic variants to differences in organismal-level traits, including drug and toxicant responses. We performed transcriptomic analysis on 207 genetically distinct C. elegans wild strains to study natural regulatory variation of gene expression. Using this massive dataset, we performed genome-wide association mappings to investigate the genetic basis underlying gene expression variation and revealed complex genetic architectures. We found a large collection of hotspots enriched for expression quantitative trait loci across the genome. We further used mediation analysis to understand how gene expression variation could underlie organism-level phenotypic variation for a variety of complex traits. These results reveal the natural diversity in gene expression and possible regulatory mechanisms in this keystone model organism, highlighting the promise of gene expression variation in shaping phenotypic diversity.

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From QTL to gene: C. elegans facilitates discoveries of the genetic mechanisms underlying natural variation

Cited by 57 publications

References 172 publications

Evaluating the power and limitations of genome-wide association mapping in C. elegans

Evaluating the power and limitations of genome-wide association mapping in C. elegans

An atlas of gene expression variation across the Caenorhabditis elegans species

Zinc Toxicity and Tolerance in Plants

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