The background puzzle: how identical mutations in the same gene lead to different disease symptoms

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20 Citations (Scopus)

Abstract

Identical disease-causing mutations can lead to different symptoms in different people. The reason for this has been a puzzling problem for geneticists. Differential penetrance and expressivity of mutations has been observed within individuals with different and similar genetic backgrounds. Attempts have been made to uncover the underlying mechanisms that determine differential phenotypic effects of identical mutations through studies of model organisms. From these studies evidence is accumulating that to understand disease mechanism or predict disease prevalence, an understanding of the influence of genetic background is as important as the putative disease-causing mutations of relatively large effect. This review highlights current insights into phenotypic variation due to gene interactions, epigenetics and stochasticity in model organisms, and discusses their importance for understanding the mutational effect on disease symptoms.
Original languageEnglish
Pages (from-to)3362-3373
JournalFEBS Journal
Volume284
Issue number20
Early online date10 May 2017
DOIs
Publication statusPublished - 16 Oct 2017

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Genes
Mutation
Penetrance
Epigenomics
Genetic Background

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The background puzzle: how identical mutations in the same gene lead to different disease symptoms. / Kammenga, Jan E.

In: FEBS Journal, Vol. 284, No. 20, 16.10.2017, p. 3362-3373.

Research output: Contribution to journalArticleAcademicpeer-review

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