Authors: Benson, Mikael; Breitling, Rainer

Source: Current Molecular Medicine, Volume 6, Number 6, September 2006 , pp. 695-701(7)

Publisher: Bentham Science Publishers

Abstract:

Complex diseases, such as allergy, diabetes and obesity depend on altered interactions between multiple genes, rather than changes in a single causal gene. DNA microarray studies of a complex disease often implicate hundreds of genes in the pathogenesis. This indicates that many different mechanisms and pathways are involved. How can we understand such complexity? How can hypotheses be formulated and tested?

One approach is to organize the data in network models and to analyze these in a top-down manner. Globally, networks in nature are often characterized by a small number of highly connected nodes, while the majority of nodes have few connections. The highly connected nodes serve as hubs that affect many other nodes. Such hubs have key roles in the network. In yeast cells, for example, deletion of highly connected proteins is associated with increased lethality, compared to deletion of less connected proteins.

This suggests the biological relevance of networks. Moving down in the network structure, there may be sub-networks or modules with specific functions. These modules may be further dissected to analyze individual nodes. In the context of DNA microarray studies of complex diseases, geneinteraction networks may contain modules of co-regulated or interacting genes that have distinct biological functions. Such modules may be linked to specific gene polymorphisms, transcription factors, cellular functions and disease mechanisms. Genes that are reliably active only in the context of their modules can be considered markers for the activity of the modules and may thus be promising candidates for biomarkers or therapeutic targets.

This review aims to give an introduction to network theory and how it can be applied to microarray studies of complex diseases.

Keywords: DNA microarray; Repressor Molecule Z; Gene A; hub proteins; co-expression

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156652406778195044

Affiliations: 1: Department of Pediatrics, Queen Silvia Children's Hospital, SE-41685 Gothenburg, Sweden.

Publication date: 2006-09-01

More about this publication?

• Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

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