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Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme

Raphaël Kiekens UGent, Annelies Vercauteren UGent, Beatrijs Moerkerke UGent, Els Goetghebeur UGent, Hilde Van Den Daele UGent, Roel Sterken UGent, Martin Kuiper UGent, Fred van Eeuwijk and Marnik Vuylsteke UGent (2006) NUCLEIC ACIDS RESEARCH. 34(13). p.3677-3686
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
HUMAN GENE-EXPRESSION, CONSTRUCTION, IDENTIFICATION, TRANSCRIPTIONAL REGULATION, ARABIDOPSIS-THALIANA, FUNCTIONAL GENOMICS, SEQUENCE TAGS, MICROARRAY, MODEL, ALLELIC VARIATION
journal title
NUCLEIC ACIDS RESEARCH
Nucleic Acids Res.
volume
34
issue
13
pages
3677 - 3686
Web of Science type
Article
Web of Science id
000240583100018
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
6.317 (2006)
JCR rank
36/259 (2006)
JCR quartile
1 (2006)
ISSN
0305-1048
DOI
10.1093/nar/gkl510
language
English
UGent publication?
yes
classification
A1
additional info
correction published in Nucleic Acids Res. (2007) 35(3), 1038 ; DOI 10.1093/nar/gkm007
copyright statement
I have retained and own the full copyright for this publication
id
351158
handle
http://hdl.handle.net/1854/LU-351158
date created
2006-11-08 10:15:00
date last changed
2017-03-02 10:04:04
@article{351158,
  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.},
  author       = {Kiekens, Rapha{\"e}l and Vercauteren, Annelies and Moerkerke, Beatrijs and Goetghebeur, Els and Van Den Daele, Hilde and Sterken, Roel and Kuiper, Martin and van Eeuwijk, Fred and Vuylsteke, Marnik},
  issn         = {0305-1048},
  journal      = {NUCLEIC ACIDS RESEARCH},
  keyword      = {HUMAN GENE-EXPRESSION,CONSTRUCTION,IDENTIFICATION,TRANSCRIPTIONAL REGULATION,ARABIDOPSIS-THALIANA,FUNCTIONAL GENOMICS,SEQUENCE TAGS,MICROARRAY,MODEL,ALLELIC VARIATION},
  language     = {eng},
  number       = {13},
  pages        = {3677--3686},
  title        = {Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme},
  url          = {http://dx.doi.org/10.1093/nar/gkl510},
  volume       = {34},
  year         = {2006},
}

Chicago
Kiekens, Raphaël, Annelies Vercauteren, Beatrijs Moerkerke, Els Goetghebeur, Hilde Van Den Daele, Roel Sterken, Martin Kuiper, Fred van Eeuwijk, and Marnik Vuylsteke. 2006. “Genome-wide Screening for Cis-regulatory Variation Using a Classical Diallel Crossing Scheme.” Nucleic Acids Research 34 (13): 3677–3686.
APA
Kiekens, R., Vercauteren, A., Moerkerke, B., Goetghebeur, E., Van Den Daele, H., Sterken, R., Kuiper, M., et al. (2006). Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme. NUCLEIC ACIDS RESEARCH, 34(13), 3677–3686.
Vancouver
1.
Kiekens R, Vercauteren A, Moerkerke B, Goetghebeur E, Van Den Daele H, Sterken R, et al. Genome-wide screening for cis-regulatory variation using a classical diallel crossing scheme. NUCLEIC ACIDS RESEARCH. 2006;34(13):3677–86.
MLA
Kiekens, Raphaël, Annelies Vercauteren, Beatrijs Moerkerke, et al. “Genome-wide Screening for Cis-regulatory Variation Using a Classical Diallel Crossing Scheme.” NUCLEIC ACIDS RESEARCH 34.13 (2006): 3677–3686. Print.