Bibliographic Details
| Title: |
Validating discovered Cis-acting regulatory genetic variants: application of an allele specific expression approach to HapMap populations. |
| Authors: |
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 |
| Source: |
PLoS ONE, Vol 3, Iss 12, p e4105 (2008) |
| Publisher Information: |
Public Library of Science (PLoS), 2008. |
| Publication Year: |
2008 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
http://europepmc.org/articles/PMC2605564?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0004105 |
| Access URL: |
https://doaj.org/article/8d9b756096ea4a439a556a52109bce58 |
| Accession Number: |
edsdoj.8d9b756096ea4a439a556a52109bce58 |
| Database: |
Directory of Open Access Journals |
