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Nat Rev Genet. 2009 Feb;10(2):134-40. doi: 10.1038/nrg2502. Epub 2009 Jan 2.

Decanalization and the origin of complex disease.

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  • 1School of Integrative Biology, Goddard Building, St Lucia Campus, University of Queensland, Brisbane, Queensland 4072, Australia.


Complex genetic disease is caused by the interaction between genetic and environmental variables and is the predominant cause of mortality globally. Recognition that susceptibility arises through the combination of multiple genetic pathways that influence liability factors in a nonlinear manner suggests that a process of 'decanalization' contributes to the epidemic nature of common genetic diseases. The rapid evolution of the human genome combined with marked environmental and cultural perturbation in the past two generations might lead to the uncovering of cryptic genetic variation that is a major source of disease susceptibility.

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