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XB-ART-48853
Proc Natl Acad Sci U S A April 6, 2010; 107 (14): 6544-9.

Systematic discovery of nonobvious human disease models through orthologous phenotypes.

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


Abstract
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: [+]
Genes referenced: agtr1 agtr2 aplnr arhgap45 erg gcc2 gnat1 gsk3a gsk3b hoxa9 map2k1 mapk14 mapk7 msr1 piga ppp3r1 psma1 rab11b.1 rab43 sec23ip seh1l snai2 sox12 sox13 tbl1xr1 tcea1 twist1
GO keywords: angiogenesis
Morpholinos: sec23ip MO1 sox13 MO1

Disease Ontology terms: Waardenburg's syndrome
OMIMs: WAARDENBURG SYNDROME, TYPE 1; WS1

Article Images: [+] show captions
References:
Amberger, 2008, Pubmed [+]


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