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. Me th od ol og y/ Pr i n c i p a l F i n d i ng s: Here we apply an ASE methodwhich utilises heterozygosity within an individual to compare expression ofthe two allelesofa genein a singlecell. Weused individuals from threeHapMappopulation groupsand 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.

Validating Discovered Cis-Acting Regulatory Genetic Variants: Application of an Allele Specific Expression Approach to HapMap Populations

Andrew Fry;MANGANO, VALENTINA;
2008-01-01

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. Me th od ol og y/ Pr i n c i p a l F i n d i ng s: Here we apply an ASE methodwhich utilises heterozygosity within an individual to compare expression ofthe two allelesofa genein a singlecell. Weused individuals from threeHapMappopulation groupsand 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.
2008
Susana, Campino; Julian, Forton; Srilakshmi, Raj; T. G., Clark; A., Mohr; Sarah, Auburn; Andrew, Fry; Mangano, Valentina; Claire, Vandiedonck; Anna, Richardson; Kirk, Rockett; Dominic P., Kwiatkowski
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/839782
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