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Proc Natl Acad Sci U S A 2010 Apr 06;10714:6544-9. doi: 10.1073/pnas.0910200107.
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Systematic discovery of nonobvious human disease models through orthologous phenotypes.

McGary KL , Park TJ , Woods JO , Cha HJ , Wallingford JB , Marcotte EM .

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.

PubMed ID: 20308572
PMC ID: PMC2851946
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus
Genes referenced: agtr1 agtr2 aplnr arhgap45 erg gcc2 gsk3a gsk3b hoxa9 map2k1 mapk14 mapk7 msr1 piga ppp3r1 psma1 rab11b sec23ip seh1l snai2 sox12 sox13 tbl1xr1 tcea1 twist1
GO keywords: angiogenesis
Morpholinos: sec23ip MO1 sox13 MO1

Disease Ontology terms: Waardenburg's syndrome
Phenotypes: Xla Wt + sox13 MO (Fig.3.C) [+]

Article Images: [+] show captions
References [+] :
, On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. 2019, Pubmed