Validating discovered Cis-acting regulatory genetic variants: Application of an allele specific expression approach to HapMap populations

Susana Campino, Julian Forton, Srilakshmi Raj, Bert Mohr, Sarah Auburn, Andrew Fry, Valentina D. Mangano, Claire Vandiedonck, Anna Richardson, Kirk Rockett, Taane G. Clark, Dominic P. Kwiatkowski

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: Localising regulatory variants that control gene expression is a challenge for genome research. Several studies have recently identified non-coding polymorphisms associated with inter-individual differences in gene expression. These approaches rely on the identification of signals of association against a background of variation due to other genetic and environmental factors. A complementary approach is to use an Allele-Specific Expression (ASE) assay, which is more robust to the effects of environmental variation and trans-acting genetic factors. Methodology/Principal Findings: Here we apply an ASE method which utilises heterozygosity within an individual to compare expression of the two alleles of a gene in a single cell. We used individuals from three HapMap population groups and analysed the allelic expression of genes with cis-regulatory regions previously identified using total gene expression studies. We were able to replicate the results in five of the six genes tested, and refined the cis- associated regions to a small number of variants. We also showed that by using multi-populations it is possible to refine the associated cis-effect DNA regions. Conclusions/Significance: We discuss the efficacy and drawbacks of both total gene expression and ASE approaches in the discovery of cis-acting variants. We show that the ASE approach has significant advantages as it is a cleaner representation of cis-acting effects. We also discuss the implication of using different populations to map cis-acting regions and the importance of finding regulatory variants which contribute to human phenotypic variation.

Original languageEnglish (US)
Article numbere4105
JournalPloS one
Issue number12
StatePublished - Dec 31 2008
Externally publishedYes

ASJC Scopus subject areas

  • General


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