| First Author | McGary KL | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 14 | Pages | 6544-9 |
| PubMed ID | 20308572 | Mgi Jnum | J:165068 |
| Mgi Id | MGI:4836137 | Doi | 10.1073/pnas.0910200107 |
| Citation | McGary KL, et al. (2010) Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc Natl Acad Sci U S A 107(14):6544-9 |
| abstractText | 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 phenotypes 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. |
