Monday, January 28, 2008

Getting a fix on gene expression   posted by Razib @ 1/28/2008 07:41:00 PM

A few weeks ago Kambiz of was mentioning how there's very little mention of gene expression on this weblog. Fair enough, but hey, what about this? And this paper just popped into my RSS today, so check it out, Differential Allelic Expression in the Human Genome: A Robust Approach to Identify Genetic and Epigenetic Cis-Acting Mechanisms Regulating Gene Expression:
We describe a new methodology to identify individual differences in the expression of the two copies of one gene. This is achieved by comparing the mRNA level of the two alleles using a heterozygous polymorphism in the transcript as marker. We show that this approach allows an exhaustive survey of cis-acting regulation in the genome: we can identify allelic expression differences due to epigenetic mechanisms of gene regulation (e.g. imprinting or X-inactivation) as well as differences due to the presence of polymorphisms in regulatory elements. The direct comparison of the expression of both alleles nullifies possible trans-acting regulatory effects (that influence equally both alleles) and thus complements the findings from gene expression association studies. Our approach can be easily applied to any cohort of interest for a wide range of studies. It notably allows following-up association signals and testing whether a gene sitting on a particular haplotype is over- or under-expressed; or can be used for screening cancer tissues for aberrant gene expression due to newly arisen mutations or alteration of the methylation patterns.

This is a provisional paper, so one assumes there will be some revisions. In any case, cancer is important & all, but this is the kind of stuff I'm interested in (see Discussion):
...We tested 56 genes for association of differential allelic expression patterns observed with a cis-acting regulatory polymorphism using genotypes generated by the HapMap project...For 23 of these genes we identified a region statistically associated with differences in allele expression that could indicate the existence of a regulatory haplotype (i.e., a region of one chromosome likely containing the polymorphism(s) causing the differential cis-regulation). These regions are often tens of kb long, consistent with previous descriptions of the linkage disequilibrium patterns in humans....

Related: Kambiz has a post up on this with a lot more commentary, Identifying Cis-Acting Elements that regulate Human Gene Expression. Also, in Nature, Genome-wide analysis of transcript isoform variation in humans.