Imprinted genes are marked in the germline and retain molecular memory of their 
parental origin, resulting in allelic expression differences during development. 
Abnormalities in imprinted inheritance occur in several genetic diseases and 
cancer, and are exemplified by the diverse genetic defects involving chromosome 
15q11-q13 in Prader-Willi (PWS) and Angelman (AS) syndromes. PWS involves loss 
of function of multiple paternally expressed genes, while mutations in a single 
gene, UBE3A, which is subject to spatially restricted imprinting, occur in some 
AS patients. Identification of mutations in the imprinting process in PWS and AS 
has led to a definition of an imprinting center (IC), involving the promoter (in 
PWS) or an alternative transcript of the SNRPN gene (in AS). The IC regulates 
initiation of imprint switching for all genes in a 2 Mb imprinted domain during 
gametogenesis. Imprinting mutations define a novel mechanism of genetic disease 
because they have no direct effect in the affected patient but, rather, it is 
the parental germline effect of an IC mutation that leads to disease in the 
offspring.