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Park, Tae Joo
Developmental Morphogenesis Lab
Research Interests
  • Morphogenesis, chondrogenesis, ciliogenesis

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Systematic discovery of nonobvious human disease models through orthologous phenotypes

Cited 98 times inthomson ciCited 93 times inthomson ci
Title
Systematic discovery of nonobvious human disease models through orthologous phenotypes
Author
McGary, Kriston L.Park, Tae JooWoods, John O.Cha, Hye JiWallingford, John B.Marcotte, Edward M.
Keywords
Angiogenesis; Bioinformatics; Evolution; Gene-phenotype associations; Homology
Issue Date
2010-04
Publisher
NATL ACAD SCIENCES
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.14, pp.6544 - 6549
Abstract
Biologists have long usedmodel organisms to study human diseases, particularlywhen themodel 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 thesemodels, 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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DOI
10.1073/pnas.0910200107
ISSN
0027-8424
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BME_Journal Papers
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