Fine-Scale Crossover Rate Variation on the<i>Caenorhabditis elegans</i>X Chromosome

Bernstein, Max R.; Rockman, Matthew V.

doi:10.1534/g3.116.028001

Cited by 29 publications

(30 citation statements)

References 63 publications

(74 reference statements)

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“…; Zdraljevic et al. ) and 16 strains from the Bernstein panel of Near Isogenic Lines (Bernstein and Rockman ). Details of strain construction are provided in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

“…We used 282 strains from the Andersen panel of Recombinant Inbred Advanced Intercross Lines Zdraljevic et al 2017) and 16 strains from the Bernstein panel of Near Isogenic Lines (Bernstein and Rockman 2016). Details of strain construction are provided in the Supporting Information.…”

Section: Strainsmentioning

confidence: 99%

“…To characterize the genetic architecture of complex trait variation in C. elegans , we used a sensitizing condition, excess of the metal nickel, to expose variation that might not be visible under favorable laboratory conditions, and we measured individual and population growth rates in animals from two recombinant panels: a large set of recombinant inbred advanced intercross lines (RIAILs) from a cross of strains N2 and CB4856 (Andersen et al. ), and a collection of near‐isogenic lines (NILs) carrying small regions of CB4856 donor genome on the X chromosome within an otherwise N2 background (Bernstein and Rockman ) (Fig. ).…”

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confidence: 99%

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Tightly linked antagonistic-effect loci underlie polygenic phenotypic variation inC. elegans

et al. 2019

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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.

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“…; Zdraljevic et al. ) and 16 strains from the Bernstein panel of Near Isogenic Lines (Bernstein and Rockman ). Details of strain construction are provided in the Supporting Information.…”

Section: Methodsmentioning

confidence: 99%

Section: Strainsmentioning

confidence: 99%

mentioning

confidence: 99%

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Tightly linked antagonistic-effect loci underlie polygenic phenotypic variation inC. elegans

et al. 2019

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“…Under this polygenic model, any region of the genome is likely to harbor phenotypically penetrant variants. We used a panel of 16 Near Isogenic Lines to test 15 consecutive intervals of 53-148 kb (that is, ~0.001 of the 100 Mb genome) spread along a 1.4 Mb region on the X chromosome (Bernstein and Rockman, 2016). Among the RIAILs, this region exhibits elevated but non-significant linkage to demographic traits (Figure 2A).…”

Section: Near Isogenic Lines Provide a Direct Test Of A Polygenic Arcmentioning

confidence: 99%

“…We used a sensitizing condition, excess of the metal nickel, to expose variation that might not be visible under favorable laboratory conditions, and we measured individual and population growth rates as a multivariate phenotype. We assayed a large set of recombinant inbred advanced intercross lines (RIAILs; Andersen et al, 2015) from a cross of strains N2 and CB4856, and a collection of NILs carrying small regions of CB4856 donor genome on the X chromosome within an otherwise N2 background (Bernstein and Rockman, 2016) (Figure 1…”

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confidence: 99%

Tightly-linked antagonistic-effect loci underlie polygenic demographic variation inC. elegans

Bernstein

Zdraljevic²,

Andersen³

et al. 2018

Preprint

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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. This view is hard to reconcile with the experience of researchers who define gene functions using mutagenesis, comparing mutants one at a time to the wild type. Here, we use the approach of experimental genetics to show that indeed, most genomic regions carry variants with detectable effects on complex traits. We used high-throughput phenotyping to characterize demography as a multivariate trait in growing populations of Caenorhabditis elegans sensitized by nickel stress. We show that demography under these conditions is genetically complex in a panel of recombinant inbred lines. We then focused on a 1.4-Mb region of the X chromosome. When we compared two near isogenic lines (NILs) that differ only at this region, they were phenotypically indistinguishable. When we used additional NILs to subdivide the region into fifteen intervals, each encompassing ~0.001 of the genome, we found that eleven of intervals have significant effects. These effects are often similar in magnitude to those of genome-wide significant QTLs mapped in the recombinant inbred lines but are antagonized by the effects of variants in adjacent intervals. Contrary to the expectation of small additive effects, our findings point to largeeffect variants whose effects are masked by epistasis or linkage disequilibrium between alleles of opposing effect.

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