Uniparental disomy
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Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copies from the other parent.[1] UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent (an earlier stage meiosis I error) or isodisomy, in which a single chromosome from one parent is duplicated (a later stage meiosis II error).[2] Because it may lead to the duplication of lethal recessive genes, isodisomy is potentially dangerous, while heterodisomy is essentially benign.
Pathophysiology
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 two (different) homologous chromosomes (inherited from both grandparents) from one parent, this is called an heterodisomic UPD. Heterodisomy (heterozygous) indicates a meiosis I error.
- When the child receives two (identical) replica copies of a single homolog of a chromosome, this is called an isodisomic UPD. Isodisomy (homozygous) indicates either a meiosis II or postzygotic chromosomal duplication.
Phenotype
Most occurrences of UPD result in no phenotypical anomalies. However, if the UPD causing event happens during meiosis II, 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. Though few imprinted genes have been identified, 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.[3]
- 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.[4][5]
- UPD has rarely been studied prospectively, with most reports either focusing on known conditions or incidental findings. It has been proposed that the incidence may not be as low as conceived, rather may be underreported.[6]
All chromosomes (uniparental diploidy)
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.[citation needed] Neither condition ever results in a liveborn infant.
History
The first clinical case of UPD was reported in 1988 and involved a girl with cystic fibrosis and unusually short stature who carried two copies of maternal chromosome 7.[7] Since 1991, out of the 47 possible disomies, 29 have been identified among individuals ascertained for medical reasons. This includes chromosomes 2, 5–11, 13–16, 21 and 22.
See also
References
- ^ Robinson WP (May 2000). "Mechanisms leading to uniparental disomy and their clinical consequences". Bioessays. 22 (5): 452–9. doi:10.1002/(SICI)1521-1878(200005)22:5<452::AID-BIES7>3.0.CO;2-K. PMID 10797485.
- ^ Human Molecular Genetics 3. Garland Science. p. 58. ISBN 0-8153-4183-0.
- ^ [1], Angelman Syndrome, Online Mendelian Inheritance in Man
- ^ Template:OMIM2
- ^ Template:DiseasesDB2
- ^ Bhatt, Arpan; Liehr, Thomas; Bakshi, Sonal R. (2013). "Phenotypic spectrum in uniparental disomy: Low incidence or lack of study". Indian Journal of Human Genetics. 19 (3): 131–34.
{{cite journal}}: Cite has empty unknown parameter:|1=(help) - ^ Spence JE, Perciaccante RG, Greig GM, Willard HF, Ledbetter DH, Hejtmancik JF, Pollack MS, O'Brien WE, Beaudet AL (1988). "Uniparental disomy as a mechanism for human genetic disease". American Journal of Human Genetics. 42 (2): 217–226. PMC 1715272. PMID 2893543.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
- Uniparental disomy (University of British Columbia)
- T. Liehr: Cases with uniparental disomy
This article incorporates public domain text from The U.S. National Library of Medicine