Genomic alterations can affect gene regulation via chromosome conformation. (A) Chromatin folding plays an essential role in transcriptional control by distally located regulatory elements. (B) Disease-associated single nucleotide polymorphisms located in distal regulatory elements can influence long-range chromatin interactions through their detrimental effect on the recruitment of TF complexes (eg, by destroying a TF binding motif), resulting in reduced expression of the target gene. (C) Chromosomal aberrations (eg, translocations) can relocate distal enhancers near a disease-associated gene, leading to the formation of pathological long-range chromatin interactions that ectopically activate the expression of this gene.