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.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.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 publication

DOI

10.1371/journal.pone.0004105

Type

Journal article

Journal

PloS one

Publication Date

01/2008

Volume

3

Addresses

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. sc11@sanger.ac.uk

Keywords

Humans, Chromosome Mapping, Genomics, Gene Expression Regulation, Regulatory Sequences, Nucleic Acid, Haplotypes, Polymorphism, Single Nucleotide, Alleles, Genome, Human, Genetic Variation