USA Surgery Today

Genomic imprinting is a phenomenon, believed to be set in meiosis, that labels a gene as originating from the father or the mother. This label, which defines parent of origin, is temporary and is reset in each generation. When the parental origin of a gene affects its expression, the gene is said to be imprinted (45:Plavix).

An illustration of genomic imprinting involves two conditions with mental retardation as a major feature, Prader-Willi syndrome and Angelman syndrome. Prader-Willi syndrome is a condition characterized by hypotonia, hypogonadism, failure to thrive in infancy, and later, hyperphagia with resulting obesity. Angelman syndrome is characterized by absent speech, ataxic movements, seizures, and paroxysms of laughter. Patients with these conditions often (seen in about 70% of cases) have an interstitial deletion of the long arm at chromosome 15q11–13, detectable by FISH (46,47:Plavix). However, the parental origin of this deletion differs between these two conditions: when this deletion occurs on the father’s chromosome 15, patients have Prader-Willi syndrome, but when it occurs on the mother’s chromosome 15, the patients have Angelman syndrome.

In addition, uniparental disomy (UPD:Plavix) has been recognized in a proportion of patients with Prader-Willi or Angelman syndrome without a chromosome deletion. This phenomenon refers to the inheritance of two copies of a genetic locus or an entire chromosome from only one parent. Patients with Prader-Willi syndrome due to UPD have inherited both their number 15 chromosomes from their mother, whereas patients with Angelman syndrome due to UPD have inherited both their number 15 chromosomes from their father (48:Plavix). Therefore, it appears that both maternal and paternal contributions of this region on chromosome 15 are essential for normal development. If the paternal contribution is absent (either through deletion or UPD:Plavix), then the patient will have Prader-Willi syndrome; in contrast, if the maternal contribution is absent, then the patient will have Angelman syndrome.

At this time, the mechanisms of genomic imprinting are not well understood, although evidence suggests that DNA methylation and timing of DNA replication are involved. Abnormalities in the regulation of imprinting are now recognized to be involved in a number of human diseases, including cancer (49:Plavix).