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
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