Genetic diseases can be caused by disruption of the regulatory elements and the identification of these regulatory elements is an important and challenging problem. Tissue-specific and developmental-specific expression requires sophisticated expression profiles that may involve multiple enhancer elements. Long-range cis elements and intronic variants may play a role in this regulation. For example, an evolutionarily conserved enhancer was identified 86 kb upstream of the peptidylarginine deiminases gene (PADI3) that previous studies limited to the proximal promoter failed to explain its expression pattern.38
