Parental Imprinting and Human Disease

Parental imprinting is a process that results in allele-specific differences in transcription, DNA methylation, and DNA replication timing. Imprinting plays an important role in development, and its deregulation can cause certain defined disease states. Absence of a paternal contribution to chromosome 15q11-q13, due to hemizygous deletion or uniparental disomy, results in the Prader-Willi syndrome. The absence of a normal maternal copy of the same region causes Angelman syndrome. The Beckwith-Wiedemann syndrome is associated with the failure of normal biparental inheritance of chromosome 11p15, and loss of imprinting is observed in several cancers including Wilms' tumor. The study of the molecular basis of abnormal imprinting in these disorders will facilitate the identification and characterization of other imprinted human disease loci.