The role of DNA methylation in human diseases was first explored in the context of genomic imprinting. Genetic imprinting is an epigenetic phenomenon in which the maternal and paternal alleles are expressed in a parent-of-origin-specific manner. Genomic imprinting is stable and heritable during mitosis. A relatively well-studied imprinting locus in humans is the insulin-like growth factor 2 (IGF2)/H19 region, located on chromosome 11p15.5, in which DNA methylation on the imprinting control region (ICR) regulates the binding of zinc-finger CCCTC-binding factor (CTCF) and subsequent gene expression. Loss of imprinting (LOI) causes many disorders such as Beckwith–Wiedemann Syndrome and cancer (which will be discussed later). Similarly, LOI of paternally-inherited chromosome 15q11.2-q13 is observed in Prader–Willi syndrome,and LOI of this region is also implicated in Angelman syndrome