Predicting the target genes of human enhancers by paralogy and orthology mapping of locus architecture. (A) CNE-enhancers when duplicated are retained with their target genes. Comparing the genic content of CNE-EBF containing paralogous loci in human genome and their orthologous loci in multiple fish lineages unmistakably suggests that duplicated copies of human CNE-EBF enhancer (hs230) are associated with the regulation of paralogous copies of EBF family members, i.e. EBF1, EBF3 and EBF4. (B) Unduplicated CNE-enhancer (hs529) is associated with its target gene SH3GL2 by tracing the differential loss of unrelated bystander genes among orthologous loci. Genes are color-coded. Direction of arrow depicts the direction of gene transcription. Light green vertical line depicts the position of CNE-enhancer. Horizontal black line depicts scale.