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

Campino, Susana, Forton, Julian ORCID: https://orcid.org/0000-0002-0580-0432, Srilakshmi, Raj, Mohr, Bert, Auburn, Sarah, Fry, Andrew, Mangano, Valentina D., Vandiedonck, Claire, Richardson, Anna, Rockett, Kirk, Clark, Taane G. and Kwiatkowski, Dominic P. 2008. Validating discovered Cis-acting regulatory genetic variants: Application of an allele specific expression approach to HapMap populations. PLoS ONE 3 (12) , e4105.. 10.1371/journal.pone.0004105

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of First Compliant Deposit:	9 December 2022
Last Modified:	06 Jun 2023 23:22
URI:	https://orca.cardiff.ac.uk/id/eprint/154727

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