Fig. 1
Long-range gene regulation. a An enhancer can target a gene over large genomic distances. b A genomic regulatory block (GRB) spanning a 1.9 Mb region of the human genome. This region displays high levels of non-coding conservation between the human and four vertebrate genomes, reflecting evolution over ~435 million years. The non-coding conservation peaks around IRX3, the predicted target gene in this GRB. The black vertical line and blue rectangle mark the genomic position of the obesity-associated SNPs (rs1421085 and rs9939609) from the Ragvin et al. study, and the linkage disequilibrium block around it, respectively. Each SNP falls within an enhancer that is capable of activating the expression of the IRX3 gene, shown in red. c The GRB model: conserved non-coding elements (shown in green) within a GRB contact the target gene’s promoter (shown in red) through looping and regulate its transcriptional activity in multiple contexts. SNPs in the linkage disequilibrium with regulatory elements involved in long-range gene regulation are often erroneously assigned to the nearest bystander gene, associating the wrong gene to the disease phenotype
