Uniparental disomy

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Uniparental disomy
Animation of uniparental isodisomy
Specialty Medical genetics

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, 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 stage meiosis I error) or isodisomy, in which a single chromosome from one parent is duplicated (a later stage meiosis II error). [2] Uniparental disomy may have clinical relevance for several reasons. For example, either isodisomy or heterodisomy can disrupt parent-specific genomic imprinting, resulting in imprinting disorders. Additionally, isodisomy leads to large blocks of homozygosity, which may lead to the uncovering of recessive genes, a similar phenomenon seen in inbred children of consanguineous partners. [3]

Contents

UPD has been found to occur in about 1 in 2,000 births. [4]

Pathophysiology

UPD can occur as a random event during the formation of egg cells or sperm cells or may happen in early fetal development. It can also occur during trisomic rescue.

Phenotype

Most occurrences of UPD result in no phenotypical anomalies. However, if the UPD-causing event happened 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. 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 ]

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

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

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 with cystic fibrosis and short stature who carried two copies of maternal chromosome 7. [13] 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.[ citation needed ][ needs update ]

See also

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References

  1. ↑ 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. S2CID   19446912.
  2. ↑ Human Molecular Genetics 3. Garland Science. pp.  58. ISBN   0-8153-4183-0.
  3. ↑ 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. PMC   3975066 . PMID   24356988.
  4. ↑ 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. ISSN   0002-9297. PMC   6848996 . PMID   31607426.
  5. 1 2 3 4 "Meiosis: Uniparental Disomy" . Retrieved 29 February 2016.
  6. ↑ Angelman Syndrome, Online Mendelian Inheritance in Man
  7. ↑ "OMIM Entry - # 608149 - KAGAMI-OGATA SYNDROME". omim.org. Retrieved 1 September 2020.
  8. ↑ Duncan, Malcolm (1 September 2020). "Chromosome 14 uniparental disomy syndrome information Diseases Database". www.diseasesdatabase.com. Retrieved 1 September 2020.
  9. ↑ 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 . PMC   3841555 . PMID   24339543. Archived from the original on 2014-02-20.{{cite journal}}: CS1 maint: unfit URL (link)
  10. ↑ 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 . ISSN   1868-7083. PMC   5640928 . PMID   29046733.
  11. ↑ 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. ISSN   0021-7743. PMID   7400781.
  12. ↑ 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.
  13. ↑ 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.

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