Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Measuring cis-acting regulatory variants genome-wide: new insights into expression genetics and disease susceptibility | Genome Medicine Minireview Measuring cis-acting regulatory variants genome-wide new insights into expression genetics and disease susceptibility Wolfgang Sadee Address Program in Pharmacogenomics College of Medicine The Ohio State University Columbus OH 43210 USA. Email Abstract Regulatory polymorphisms have emerged as a prevalent source of phenotypic variability capable of driving rapid evolution. mRNA profiling combined with genome-wide genotyping of polymorphisms has revealed pervasive genetic influences on gene expression acting both in cis and in trans. Measuring allelic ratios of RNA transcripts makes it possible to focus on cis-acting factors separately from trans-acting processes. Using large-scale allelic expression analysis a recent study by Ge and colleagues demonstrates a high incidence of cis-acting regulatory variants promising insights into the missing herita-bility component of complex disorders. Here I evaluate their results and discuss the limitations of the current approach and avenues for exploring disease risk guiding successful therapy early intervention and prevention. Introduction Advances in large-scale genotyping and DNA sequencing have yielded unprecedented insights into human genomic diversity and yet a large proportion of genetic risk factors for complex human diseases remains unknown. How can we shed light on the missing heritability 1 Whereas genetics has traditionally focused on nonsynonymous polymorphisms that alter the encoded amino acid sequence coding single nucleotide polymorphisms SNPs the term SNP is used here for all variants the focus has now shifted to regulatory variants rSNPs which are likely to be more prevalent than coding SNPs. Suspected as being a primary driver of evolution 2-4 rSNPs can undergo positive selection potentially reaching high frequency. Intense exploration of regulatory variants has been accelerated by new genomic technologies. Here I discuss the findings of a recent genome-wide
