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Resources » Paper

Vu V et al. (2015) Cell "Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes."

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  • Comments on Vu V et al. (2015) Cell "Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes." (0)

  • Overview

    PMID:
    26186192
    DOI:
    10.1016/j.cell.2015.06.037
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00047114

    Vu V, Verster AJ, Schertzberg M, Chuluunbaatar T, Spensley M, Pajkic D, Hart GT, Moffat J, & Fraser AG (2015). Natural Variation in Gene Expression Modulates the Severity of Mutant Phenotypes. Cell, 162, 391-402. doi:10.1016/j.cell.2015.06.037

    Many mutations cause genetic disorders. However, two people inheriting the same mutation often have different severity of symptoms, and this is partly genetic. The effects of genetic background on mutant phenotypes are poorly understood, but predicting them is critical for personalized medicine. To study this phenomenon comprehensively and systematically, we used RNAi to compare loss-of-function phenotypes for 1,400 genes in two isolates of C. elegans and find that 20% of genes differ in the severity of phenotypes in these two genetic backgrounds. Crucially, this effect of genetic background on the severity of both RNAi and mutant phenotypes can be predicted from variation in the expression levels of the affected gene. This is also true in mammalian cells, suggesting it is a general property of genetic networks. We suggest that differences in the manifestation of mutant phenotypes between individuals are largely the result of natural variation in gene expression.

    Authors: Vu V, Verster AJ, Schertzberg M, Chuluunbaatar T, Spensley M, Pajkic D, Hart GT, Moffat J, Fraser AG


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