Edgotype: a fundamental link between genotype and phenotype.

Gene Regulatory Networks; Genetic Association Studies/methods; Genetic Predisposition to Disease/genetics; Genotype; Humans; Metabolic Networks and Pathways/genetics; Models, Genetic; Mutation; Phenotype; Protein Interaction Domains and Motifs/genetics

Abstract :

[en] Classical 'one-gene/one-disease' models cannot fully reconcile with the increasingly appreciated prevalence of complicated genotype-to-phenotype associations in human disease. Genes and gene products function not in isolation but as components of intricate networks of macromolecules (DNA, RNA, or proteins) and metabolites linked through biochemical or physical interactions, represented in 'interactome' network models as 'nodes' and 'edges', respectively. Accordingly, mechanistic understanding of human disease will require understanding of how disease-causing mutations affect systems or interactome properties. The study of 'edgetics' uncovers specific loss or gain of interactions (edges) to interpret genotype-to-phenotype relationships. We review how distinct genetic variants, the genotype, lead to distinct phenotypic outcomes, the phenotype, through edgetic perturbations in interactome networks altogether representing the 'edgotype'.

Disciplines :

Genetics & genetic processes

Author, co-author :

Sahni, Nidhi

Yi, Song

Zhong, Quan

Jailkhani, Noor

CHARLOTEAUX, Benoit ; Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

Cusick, Michael E.

Vidal, Marc

Language :

English

Title :

Edgotype: a fundamental link between genotype and phenotype.

Publication date :

2013

Journal title :

Current opinion in genetics & development

ISSN :

0959-437X

eISSN :

1879-0380

Volume :

Issue :

Pages :

649-57

Peer reviewed :

Peer reviewed

Commentary :

Available on ORBi :

since 22 August 2019

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Scopus citations^®

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116

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