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To what extent can variation in phenotypic traits such as disease risk be accurately predicted in individuals? In this Review, I highlight recent studies in model organisms that are relevant both to the challenge of accurately predicting phenotypic variation from individual genome sequences ('whole-genome reverse genetics') and for understanding why, in many cases, this may be impossible. These studies argue that only by combining genetic knowledge with in vivo measurements of biological states will it be possible to make accurate genetic predictions for individual humans.
 
Perturbation of overlapping modules of orthologous genes may result in one set of phenotypes in one organism but a different set of phenotypes in another organism. a | For example, mutations in a module of DNA damage response genes cause breast cancer in humans but a high incidence of males (Him) phenotype in Caenorhabditis elegans (owing to chromosome non-dysjunction). Other genes linked to the Him phenotype therefore make good candidate genes for novel breast cancer loci. b | The overlap in the sets of genes linked to vascular growth in vertebrates and to cell-wall maintenance in yeast allowed the prediction that the approved antifungal drug thiabendazole would act as an angiogenesis inhibitor
Read the paper:http://www.nature.com/nrg/journal/v14/n3/abs/nrg3404.html