Uniparental disomy

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development. It can also occur during trisomic rescue. When the child receives the (two) homologous chromosomes (inherited from both grandparents) from one parent, this is called an heterodisomic UPD. When the child receives, two (identical) replica copies of a single homolog of a chromosome, this is called an isodisomic UPD. Heterodisomy (Heterozygous) indicates a meiosis I error, whereas isodisomy (homozygous) indicates either a meiosis II error or postzygotic duplication.

Most occurrences of UPD result in no phenotypical anomalies. However, if the UPD causing event happens during meiosis I, the genotype may include identical copies of the uniparental chromosome (isodisomy), leading to the manifestation of rare recessive disorders. UPD should be suspected in an individual manifesting a recessive disorder, where only one parent is a carrier.

Uniparental inheritance of imprinted genes can also result in phenotypical anomalies. Few imprinted genes have been identified, however uniparental inheritance of an imprinted gene can result in the loss of gene function which can lead to delayed development, mental retardation, or other medical problems. The most well-known conditions include Prader-Willi syndrome and Angelman syndrome. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann syndrome, are associated with abnormalities of imprinted genes on the short arm of chromosome 11. Chromosome 14 is also known to cause particular symptoms such as skeletal abnormalities, mental retardation and joint contractures among others.

Occasionally, all chromosomes will be inherited from one parent, due to either a sperm fertilizing an empty egg and duplicating itself, or a diploid egg that is not fertilized. The effect is similar to triploidy, with either a molar pregnancy with no embryo if only paternal genes are present, or an embryo with no placenta if only maternal genes are present. Neither condition ever results in a liveborn infant.

The first clinical case of UPD was reported in 1991 and involved a girl with cystic fibrosis and unusually short stature who carried two copies of maternal chromosome 7. Since 1991, out of the 47 possible disomies, 29 have been identified among individuals ascertained for medical reasons. This includes Chromosome 2, 5-11, 13-16, 21 and 22.