Dissecting the eQTL Micro-Architecture in Caenorhabditis elegans

Sterken, M.G.; Bevers, R.; Volkers, Rita J. M.; Riksen, J.A.G.; Kammenga, J.E.; Snoek, L. Basten

doi:10.3389/fgene.2020.501376

Cited by 15 publications

(19 citation statements)

References 89 publications

(159 reference statements)

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“…We first tested whether the data were structured as expected based on literature. Namely, the HS effect was expected to be larger than the strain effect, and the strain effect was expected to be larger than the effect of infection with Orsay virus [15,23,29]. Indeed, by using correlation analysis and principal component analysis, we saw that the data clustered as expected (Figure S2a,b).…”

Section: Candidate Genes Selected Underlying Combined Viral Sensitivity and Hssupporting

confidence: 51%

“…For the HS experiment, the temperature was set to 35 • C for 2 h in a climate cabinet (Elbanton) because it would trigger the HSR without killing the worm [15], which is necessary for later OrV infection. First, bleached eggs were hatched at 20 • C and grown for 20 h. Subsequently, for the control treatment, the OrV infection started after 23 h. For the HS-OrV treatment, from 20 h, the worms were grown at HS (35 • C for 2 h), after which they were allowed to recover (20 • C for 1 h).…”

Section: Orv Infection and Hs Experimentsmentioning

confidence: 99%

“…To explore the potential genes associated with lower OrV susceptibility after HS, the global gene expression profile was measured using microarray analysis. Gene expression was measured in the strains N2 and CB4856, as these genotypes have been well-studied in regard to their gene-expression responses to temperature changes and HS [15][16][17]. Although the microarrays were originally designed for the N2 strain, they can be used for the CB4856 strain [18,19].…”

Section: Microarray Experimentsmentioning

confidence: 99%

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Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection

Huang

Sterken

Zwet

et al. 2021

Genes

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The nematode Caenorhabditis elegans has been a versatile model for understanding the molecular responses to abiotic stress and pathogens. In particular, the response to heat stress and virus infection has been studied in detail. The Orsay virus (OrV) is a natural virus of C. elegans and infection leads to intracellular infection and proteostatic stress, which activates the intracellular pathogen response (IPR). IPR related gene expression is regulated by the genes pals-22 and pals-25, which also control thermotolerance and immunity against other natural pathogens. So far, we have a limited understanding of the molecular responses upon the combined exposure to heat stress and virus infection. We test the hypothesis that the response of C. elegans to OrV infection and heat stress are co-regulated and may affect each other. We conducted a combined heat-stress-virus infection assay and found that after applying heat stress, the susceptibility of C. elegans to OrV was decreased. This difference was found across different wild types of C. elegans. Transcriptome analysis revealed a list of potential candidate genes associated with heat stress and OrV infection. Subsequent mutant screens suggest that pals-22 provides a link between viral response and heat stress, leading to enhanced OrV tolerance of C. elegans after heat stress.

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Section: Candidate Genes Selected Underlying Combined Viral Sensitivity and Hssupporting

confidence: 51%

Section: Orv Infection and Hs Experimentsmentioning

confidence: 99%

Section: Microarray Experimentsmentioning

confidence: 99%

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Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection

Huang

Sterken

Zwet

et al. 2021

Genes

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“…We used the IL CB4856 population to test the QTL for the expression of clec-62 , for which multiple QTL were uncovered in a previous study in the IL N2 panel (41). Expression of clec-62 was measured in a similar setup as in two previous eQTL experiments (41,42).…”

Section: Methodsmentioning

confidence: 99%

Two sides to every coin: reciprocal introgression line populations inCaenorhabditis elegans

Sterken

Sluijs

Creij

et al. 2022

Preprint

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Quantitative genetics seeks to understand the role of allelic variation in trait differences. Introgression lines (ILs) contain a single genetic locus introgressed into another genetic background, and are one of the most powerful quantitative trait locus (QTL) mapping designs. However, albeit useful for QTL discovery, this homogenous background confounds genetic interactions. Here, we created a novel IL population, complementary to a previously created population, which enables identification of genetic interactions in ILs. The novel ILCB4856 panel was made by crossing divergent strains of the model nematode Caenorhabditis elegans (N2 and CB4856). The ILCB4856 panel comprises a population of 145 strains with sequencing confirmed N2 introgressions in a CB4856 background from which a core set of 87 strains covering the entire genome was selected. We present three experiments demonstrating the power of the complementary IL panels. First, we performed QTL mapping identifying new regions associated with lifespan. Second, the existence of opposite-effect loci regulating heat-stress survival is demonstrated. Third, by combining ILN2 and ILCB4856 strains, an interacting expression QTL was uncovered. In conclusion, the complementary IL panels are a unique and ready-to-use resource to identify, resolve, and refine complex trait architectures in C. elegans.

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“…It is possible that such co-localized QTL were the result of a single pleiotropic modifier affecting various aspects of the C. elegans physiology. On the other hand, this might be the result of unresolved separate QTL (Dupuis & Siegmund, 1999;Gutteling et al, 2007b;Sterken et al, 2020).…”

Section: Genetic Parameters and Qtl Analysis Indicate A Complex Genetic Regulation Of Body-size Traitsmentioning

confidence: 99%

The genetic architecture underlying body-size traits plasticity over different temperatures and developmental stages inCaenorhabditis elegans

et al. 2021

Preprint

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Most ectotherms obey the temperature-size rule, meaning they grow larger in a colder environment. This raises the question of how the interplay between genes and temperature affect the body size of ectotherms. Despite the growing body of literature on the physiological life-history and molecular genetic mechanism underlying the temperature-size rule, the overall genetic architecture orchestrating this complex phenotype is not yet fully understood. One approach to identify genetic regulators of complex phenotypes is Quantitative Trait Locus (QTL) mapping. Here, we explore the genetic architecture of body size phenotypes, in different temperatures using Caenorhabditis elegans as a model ectotherm. We used 40 recombinant inbred lines (RILs) derived from N2 and CB4856, which were reared at four different temperatures (16°C, 20°C, 24°C, and 26°C) and measured at two developmental stages (L4 and adult). The animals were measured for body length, width at vulva, body volume, length/width ratio, and seven other body-size traits. The genetically diverse RILs varied in their body-size phenotypes with heritabilities ranging from 0.20 to 0.99. We detected 18 QTL underlying the body-size phenotypes across all treatment combinations, with the majority clustering on Chromosome X. We hypothesize that the Chromosome X QTL could result from a known pleiotropic regulator – npr-1 – known to affect the body size of C. elegans through behavioral changes. In conclusion, our findings shed more light on multiple loci affecting body size plasticity and allow for a more refined analysis of the temperature-size rule.

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Dissecting the eQTL Micro-Architecture in Caenorhabditis elegans

Cited by 15 publications

References 89 publications

Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection

Heat Stress Reduces the Susceptibility of Caenorhabditis elegans to Orsay Virus Infection

Two sides to every coin: reciprocal introgression line populations inCaenorhabditis elegans

The genetic architecture underlying body-size traits plasticity over different temperatures and developmental stages inCaenorhabditis elegans

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