Clinical Chemistry
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Clinical Chemistry 55: 698-708, 2009. First published February 26, 2009; 10.1373/clinchem.2008.120931
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(Clinical Chemistry. 2009;55:698-708.)
© 2009 American Association for Clinical Chemistry, Inc.

Reviews

Management of Gene Promoter Mutations in Molecular Diagnostics

Karen M. K. de Vooght1,a, Richard van Wijk1 and Wouter W. van Solinge1

1 Department of Clinical Chemistry and Haematology, Laboratory for Red Blood Cell Research, University Medical Center Utrecht, Utrecht, the Netherlands.

aAddress correspondence to this author at: Department of Clinical Chemistry and Haematology, Laboratory for Red Blood Cell Research, University Medical Center Utrecht, Postbus 85500, 3508 GA, Utrecht, the Netherlands. Fax +31 88 7555418; e-mail k.devooght{at}umcutrecht.nl.

Background: Although promoter mutations are known to cause functionally important consequences for gene expression, promoter analysis is not a regular part of DNA diagnostics.

Content: This review covers different important aspects of promoter mutation analysis and includes a proposed model procedure for studying promoter mutations. Characterization of a promoter sequence variation includes a comprehensive study of the literature and databases of human mutations and transcription factors. Phylogenetic footprinting is also used to evaluate the putative importance of the promoter region of interest. This in silico analysis is, in general, followed by in vitro functional assays, of which transient and stable transfection assays are considered the gold-standard methods. Electrophoretic mobility shift and supershift assays are used to identify trans-acting proteins that putatively interact with the promoter region of interest. Finally, chromatin immunoprecipitation assays are essential to confirm in vivo binding of these proteins to the promoter.

Summary: Although promoter mutation analysis is complex, often laborious, and difficult to perform, it is an essential part of the diagnosis of disease-causing promoter mutations and improves our understanding of the role of transcriptional regulation in human disease. We recommend that routine laboratories and research groups specialized in gene promoter research cooperate to expand general knowledge and diagnosis of gene-promoter defects.




The following articles in journals at HighWire Press have cited this article:


Home page
 Brief Funct Genomic ProteomicHome page
D. J. Epstein
Cis-regulatory mutations in human disease
Brief Funct Genomic Proteomic, July 29, 2009; (2009) elp021v1.
[Abstract] [Full Text] [PDF]


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