Expression quantitative trait loci are highly sensitive to cellular differentiation state

Gerrits, A., Li, Y., Tesson, B.M., Bystrykh, L.V., Dontje, B., Wang, X., Breitling, R. , Jansen, R.C. and de Haan, G. (2009) Expression quantitative trait loci are highly sensitive to cellular differentiation state. PLoS Genetics, 5(10), e1000692. (doi: 10.1371/journal.pgen.1000692)

Abstract

Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that, while a significant number of eQTLs (365) had a consistent “static” regulatory effect on gene expression, an even larger number were found to be very sensitive to cell stage. As many as 1,283 eQTLs exhibited a “dynamic” behavior across cell types. By looking more closely at these dynamic eQTLs, we show that the sensitivity of eQTLs to cell stage is largely associated with gene expression changes in target genes. These results stress the importance of studying gene expression variation in well-defined cell populations. Only such studies will be able to reveal the important differences in gene regulation between different cel

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Breitling, Professor Rainer
• Authors: Gerrits, A., Li, Y., Tesson, B.M., Bystrykh, L.V., Dontje, B., Wang, X., Breitling, R., Jansen, R.C., and de Haan, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: PLoS Genetics
• Publisher: Public Library of Science
• ISSN: 1553-7390
• ISSN (Online): 1553-7404
• Copyright Holders: Copyright