Uniparental disomy
| Uniparental disomy | |
|---|---|
| Animation of uniparental isodisomy | |
| Specialty | Medical genetics |
Uniparental disomy(UPD) occurs when a person receives two copies of achromosome,or of part of a chromosome, from one parent and no copy from the other.[1]UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent (an earlier stagemeiosis Ierror) orisodisomy,in which a single chromosome from one parent is duplicated (a later stagemeiosis IIerror).[2]Uniparental disomy may have clinical relevance for several reasons. For example, either isodisomy or heterodisomy can disrupt parent-specificgenomic imprinting,resulting in imprinting disorders. Additionally, isodisomy leads to large blocks ofhomozygosity,which may lead to the uncovering ofrecessivegenes, a similar phenomenon seen ininbredchildren ofconsanguineouspartners.[3]
UPD has been found to occur in about 1 in 2,000 births.[4]
Pathophysiology
[edit]UPD can occur as a random event during the formation ofegg cellsorsperm cellsor may happen in earlyfetaldevelopment. It can also occur duringtrisomic rescue.
- When the child receives two (different)homologous chromosomes(inherited from both grandparents) from one parent, this is called heterodisomic UPD.Heterodisomy(heterozygous) indicates ameiosis Ierror if the gene loci in question didn't cross over.[5]
- When the child receives two (identical) replica copies of a singlehomologueof achromosome,this is called an isodisomic UPD.Isodisomy(homozygous) indicates either ameiosis II(if the gene loci in question didn't cross over[5]) or postzygoticchromosomal duplication.
- A meiosis I error can result in isodisomic UPD if the gene loci in question crossed over, for example, a distal isodisomy would be due to duplicated gene loci from the maternal grandmother that crossed over and due to an error during meiosis I, ended up in the same gamete.[5]
- A meiosis II error can result in heterodisomy UPD if the gene loci crossed over in a similar fashion.[5]
Phenotype
[edit]Most occurrences of UPD result in nophenotypicalanomalies. However, if the UPD-causing event happened duringmeiosisII, thegenotypemay include identical copies of the uniparental chromosome (isodisomy), leading to the manifestation of rarerecessivedisorders. UPD should be suspected in an individual manifesting a recessive disorder where only one parent is acarrier.
Uniparentalinheritanceofimprintedgenes can also result in phenotypical anomalies. Although 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, intellectual disability, or other medical problems.[citation needed]
- The most well-known conditions includePrader–Willi syndromeandAngelman syndrome.Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm ofchromosome 15.[6]
- Other conditions, such asBeckwith–Wiedemann syndrome,are associated with abnormalities of imprinted genes on the short arm ofchromosome 11.
- Chromosome 14is also known to cause particular symptoms such as skeletal abnormalities,intellectual disability,and joint contractures, among others.[7][8]
UPD has rarely been studied prospectively, with most reports focusing on either known conditions or incidental findings. It has been proposed that the incidence may not be as low as believed, rather it may be under-reported.[9]
All chromosomes
[edit]Genome wide UPD, also called uniparental diploidy, is when all chromosomes are inherited from one parent. Only in mosaic form can this phenomenon be compatible with life. As of 2017, there have only been 18 reported cases of genome wide UPD.[10]
History
[edit]Eric Engel first proposed the concept of uniparental disomy in 1980 as both homologous chromosomes are inherited from one parent, with no contribution (for that chromosome) from the other parent.[11][12]Eight years later in 1988, the first clinical case of UPD was reported and involved a girl withcystic fibrosisand short stature who carried two copies of maternalchromosome 7.[13]Since 1991, out of the 47 possible disomies, 29 have been identified among individuals ascertained for medical reasons. This includeschromosomes2, 5–11, 13–16, 21 and 22.[citation needed][needs update]
See also
[edit]References
[edit]- ^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.PMID10797485.S2CID19446912.
- ^Human Molecular Genetics 3.Garland Science. pp.58.ISBN0-8153-4183-0.
- ^King DA (2013)."A novel method for detecting uniparental disomy from trio genotypes identifies a significant excess in children with developmental disorders".Genome Research.24(4): 673–687.doi:10.1101/gr.160465.113.PMC3975066.PMID24356988.
- ^Nakka, Priyanka; Smith, Samuel Pattillo; O'Donnell-Luria, Anne H.; McManus, Kimberly F.; Agee, Michelle; Auton, Adam; Bell, Robert K.; Bryc, Katarzyna; Elson, Sarah L.; Fontanillas, Pierre; Furlotte, Nicholas A. (2019-11-07)."Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population".The American Journal of Human Genetics.105(5): 921–932.doi:10.1016/j.ajhg.2019.09.016.ISSN0002-9297.PMC6848996.PMID31607426.
- ^abcd"Meiosis: Uniparental Disomy".Retrieved29 February2016.
- ^Angelman Syndrome, Online Mendelian Inheritance in Man
- ^"OMIM Entry - # 608149 - KAGAMI-OGATA SYNDROME".omim.org.Retrieved1 September2020.
- ^Duncan, Malcolm (1 September 2020)."Chromosome 14 uniparental disomy syndrome information Diseases Database".www.diseasesdatabase.com.Retrieved1 September2020.
- ^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.doi:10.4103/0971-6866.120819.PMC3841555.PMID24339543.Archived from the original on 2014-02-20.
{{cite journal}}:CS1 maint: unfit URL (link) - ^Bens, Susanne; Luedeke, Manuel; Richter, Tanja; Graf, Melanie; Kolarova, Julia; Barbi, Gotthold; Lato, Krisztian; Barth, Thomas F.; Siebert, Reiner (2017)."Mosaic genome-wide maternal isodiploidy: an extreme form of imprinting disorder presenting as prenatal diagnostic challenge".Clinical Epigenetics.9:111.doi:10.1186/s13148-017-0410-y.ISSN1868-7083.PMC5640928.PMID29046733.
- ^Engel, E. (1980-03-01)."A new genetic concept: the uniparental disomy and its potential effect, the isodisomy (author's transl)".Journal de Genetique Humaine.28(1): 11–22.ISSN0021-7743.PMID7400781.
- ^del Gaudio, Daniela; Shinawi, Marwan; Astbury, Caroline; Tayeh, Marwan K.; Deak, Kristen L.; Raca, Gordana (2020-07-01)."Diagnostic testing for uniparental disomy: a points to consider statement from the American College of Medical Genetics and Genomics (ACMG)".Genetics in Medicine.22(7): 1133–1141.doi:10.1038/s41436-020-0782-9.PMID32296163.
- ^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.PMC1715272.PMID2893543.
External links
[edit]- "Uniparental disomy".Department of Medical Genetics, University of British Columbia. Archived from the original on 2002-06-17.
{{cite web}}:CS1 maint: unfit URL (link) - T. Liehr:Cases with uniparental disomy
- UPD Animations:UPD Animations
This article incorporates public domain text fromThe U.S. National Library of Medicine