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Reverse engineering the genotype–phenotype map with natural genetic variation

Nature volume 456, pages 738–744 (2008)Cite this article

Abstract

The genetic variation that occurs naturally in a population is a powerful resource for studying how genotype affects phenotype. Each allele is a perturbation of the biological system, and genetic crosses, through the processes of recombination and segregation, randomize the distribution of these alleles among the progeny of a cross. The randomized genetic perturbations affect traits directly and indirectly, and the similarities and differences between traits in their responses to common perturbations allow inferences about whether variation in a trait is a cause of a phenotype (such as disease) or whether the trait variation is, instead, an effect of that phenotype. It is then possible to use this information about causes and effects to build models of probabilistic 'causal networks'. These networks are beginning to define the outlines of the 'genotype–phenotype map'.

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Figure 1: From genetic randomization to causal network.
Figure 2: Measurement error can confuse causal inference.

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Acknowledgements

I thank the Jane Coffin Childs Memorial Fund for Medical Research and New York University for support, and L. Chen for discussion.

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  1. Department of Biology, Center for Genomics and Systems Biology, New York University, 100 Washington Square East, New York, 10003, New York, USA

    Matthew V. Rockman

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Rockman, M. Reverse engineering the genotype–phenotype map with natural genetic variation. Nature 456, 738–744 (2008). https://doi.org/10.1038/nature07633

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