title: Genetic control of global gene expression levels in the intestinal mucosa: a human twin study.
abstract: Phenotypic variation between individuals, such as different mRNA expression levels, is influenced by genetic and nongenetic 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 nongenetic 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 monitored the level of genetic control over genomewide mRNA expression profiles in the healthy intestinal mucosa of 10 monozygotic and 10 dizygotic human twin pairs with microarray analyses. Our results, which are supported by real-time PCR and 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 nongenetic determinants of transcriptomal profiles and their influence on physiological and pathophysiological mechanisms are crucial to understanding the key role played by gene-environment interactions in health and disease.
authors.affiliation: Institute of Clinical Molecular Biology, Center for Molecular Biosciences (ZMB), Christian Albrechts University of Kiel, Kiel, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.forename: Alexander
authors.initials: A
authors.lastname: Begun
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.forename: Martin
authors.initials: M
authors.lastname: Kerick
authors.forename: Nancy
authors.initials: N
authors.lastname: Mah
authors.forename: Aida
authors.initials: A
authors.lastname: Zvirbliene
authors.forename: Martina E
authors.initials: ME
authors.lastname: Spehlmann
authors.forename: Nicole
authors.initials: N
authors.lastname: von Wurmb-Schwark
authors.forename: Limas
authors.initials: L
authors.lastname: Kupcinskas
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger