西亚试剂：Systematic discovery of nonobvious human disease models thr

Systematic discovery of nonobvious human disease models through orthologous Kriston L. McGarya,1, Tae Joo Parka,b,1, John O. Woodsa, Hye Ji Chaa, John B. Wallingforda,b, and Edward M. Marcottea,c,2

Biologists have long used model organisms to study human diseases, particularly when the model bears a close resemblance to the disease. We present a method that quantitatively and systematically identifies nonobvious equivalences between mutant s in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). These orthologous phenotypes, or phenologs, predict unique genes associated with diseases. Our method suggests a yeast model for angiogenesis defects, a worm model for breast cancer, mouse models of autism, and a plant model for the neural crest defects associated with Waardenburg syndrome, among others. Using these models, we show that SOX13 regulates angiogenesis, and that SEC23IP is a likely Waardenburg gene. Phenologs reveal functionally coherent, evolutionarily conserved gene networks—many predating the plant-animal divergence—capable of identifying candidate disease genes.

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