To study allelic gene expression globally, we reengineered the assay and analysis of the Affymetrix SNP chip so that it measures allele-specific transcript variation. We observed gene expression differences between the two chromosomes within the same individual. The relative expression of specific alleles, however, varied between individuals suggesting a dependence on genomic context. We have observed differences due to haplotypes, chromatin features, and DNA methylation status. These studies from our lab have established that allelic variation in gene expression is common throughout the human genome. In addition, our studies indicate that genetics is an important factor that influences global chromatin state mediated by histone modification, the hallmark of the epigenetic phenomena. We are currently applying the SNP array technology to study global allele-specific DNA methylation. Furthermore, we are investigating the various mechanisms, including genetic polymorphism, epigenetic modifications, and post-transcriptional processing that can regulate differential allelic gene expression. We are also extending our research by characterize allele-specific gene expression and epigenetic modifications using breast cancer cell lines and breast primary tumors. We are currently focusing on how genetic variant can mediate differential drug response.
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