title: Uncovering drug-responsive regulatory elements.
abstract: Nucleotide changes in gene regulatory elements can have a major effect on interindividual differences in drug response. For example, by reviewing all published pharmacogenomic genome-wide association studies, we show here that 96.4% of the associated single nucleotide polymorphisms reside in noncoding regions. We discuss how sequencing technologies are improving our ability to identify drug response-associated regulatory elements genome-wide and to annotate nucleotide variants within them. We highlight specific examples of how nucleotide changes in these elements can affect drug response and illustrate the techniques used to find them and functionally characterize them. Finally, we also discuss challenges in the field of drug-responsive regulatory elements that need to be considered in order to translate these findings into the clinic.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.|Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Marcelo R
authors.initials: MR
authors.lastname: Luizon
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.|Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
mesh_terms: D000818:Animals; D015894:Genome, Human / Q000187:drug effects / Q000235:genetics; D055106:Genome-Wide Association Study / Q000639:trends; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000187:drug effects* / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects / Q000235:genetics
chemical_list: D004364:Pharmaceutical Preparations
keywords: ChIP-seq; RNA-seq; enhancers; gene regulatory elements; pharmacogenomics; promoters; transcriptional regulation