Reverse engineering the genotype–phenotype map with natural genetic variation

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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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