Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

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The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2012-10
Language
English
Article Type
Article
Keywords

NATURAL-SELECTION; NETWORK; PROTEOME; GENOME; LOCALIZATION; PREDICTIONS; DISORDERS; ORTHOLOGS; DATABASE; BIOLOGY

Citation

SCIENTIFIC REPORTS, v.2

ISSN
2045-2322
DOI
10.1038/srep00757
URI
http://hdl.handle.net/10203/174471
Appears in Collection
GCT-Journal Papers(저널논문)
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