title: Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme.
abstract: Large-scale screening studies carried out to date for genetic variants that affect gene regulation are generally limited to descriptions of differences in allele-specific expression (ASE) detected in vivo. Allele-specific differences in gene expression provide evidence for a model whereby cis-acting genetic variation results in differential expression between alleles. Such gene surveys for regulatory variation are a first step in identifying the specific nucleotide changes that govern gene expression differences, but they leave the underlying mechanisms unexplored. Here, we propose a quantitative genetics approach to perform a genome-wide analysis of ASE differences (GASED). The GASED approach is based on a diallel design that is often used in plant breeding programs to estimate general combining abilities (GCA) of specific inbred lines and to identify high-yielding hybrid combinations of parents based on their specific combining abilities (SCAs). In a context of gene expression, the values of GCA and SCA parameters allow cis- and trans-regulatory changes to be distinguished and imbalances in gene expression to be ascribed to cis-regulatory variation. With this approach, a total of 715 genes could be identified that are likely to carry allelic polymorphisms responsible for at least a 1.5-fold allelic expression difference in a total of 10 diploid Arabidopsis thaliana hybrids. The major strength of the GASED approach, compared to other ASE detection methods, is that it is not restricted to genes with allelic transcript variants. Although a false-positive rate of 9/41 was observed, the GASED approach is a valuable pre-screening method that can accelerate systematic surveys of naturally occurring cis-regulatory variation among inbred lines for laboratory species, such as Arabidopsis, mouse, rat and fruitfly, and economically important crop species, such as corn.
authors.affiliation: Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent University, Technologiepark 927, B-9052 Gent, Belgium.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Kiekens
authors.forename: Annelies
authors.initials: A
authors.lastname: Vercauteren
authors.forename: Beatrijs
authors.initials: B
authors.lastname: Moerkerke
authors.forename: Els
authors.initials: E
authors.lastname: Goetghebeur
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Den Daele
authors.forename: Roel
authors.initials: R
authors.lastname: Sterken
authors.forename: Martin
authors.initials: M
authors.lastname: Kuiper
authors.forename: Fred
authors.initials: F
authors.lastname: van Eeuwijk
authors.forename: Marnik
authors.initials: M
authors.lastname: Vuylsteke
mesh_terms: D000483:Alleles; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018506:Gene Expression Regulation, Plant; D023281:Genomics / Q000379:methods*; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D050436:Regulatory Elements, Transcriptional