Submitted on January 21, 2009
Revised on March 4, 2009
Accepted on March 8, 2009
Genetic control of global gene expression levels in the intestinal mucosa - a human twin study
Robert Häsler1, Alexander Begun2, Sandra Freitag-Wolf2, Martin Kerick1, Nancy Mah1, Aida Zvirbliene3, Martina E. Spehlmann1, Nicole von Wurmb-Schwark4, Limas Kupcinskas3, Philip Rosenstiel1, and Stefan Schreiber5*
1 Institute of Clinical Molecular Biology, Center for Molecular Biosciences (ZMB)
2 Institute of Medical Informatics and Statistics, Christian Albrechts University of Kiel
3 Kaunas University of Medicine
4 Institute of Legal Medicine, Christian Albrechts University of Kiel
5 Christian-Albrechts-University of Kiel
* To whom correspondence should be addressed. E-mail: s.schreiber{at}mucosa.de.
Phenotypic variation between individuals, such as different mRNA expression levels, is influenced by genetic and non-genetic factors. Although several studies have addressed the interplay between genotypes and expression profiles in various model organisms in the recent years, the detailed and relative contributions of genetic and non-genetic factors in regulating plasticity of gene expression in barrier organs (e.g. skin, gut) which are exposed to continuous environmental challenge, are still poorly understood. Here we systematically monitor the level of genetic control over genome-wide mRNA expression profiles in the healthy intestinal mucosa of 10 monozygotic and 10 dizygotic human twin pairs using microarray analyses. Our results, which are supported by real time PCR verification and the analysis of molecular phylogenetic conservation, indicate that genes associated with energy metabolism and cell and tissue regeneration pathways are under strong genetic control. Conversely, genes associated with immune response seem to be mainly controlled by exogenous factors. Further insights into the relative extent of genetic and non-genetic determinants of transcriptomal profiles and their influence on physiological and pathophysiological mechanisms are crucial to understanding the key-role played by gene-environmentinteractions in health and disease.
