X-linked recessive inheritance

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X-linked recessive inheritance X-linked recessive (2).svg
X-linked recessive inheritance

X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily hemizygous for the gene mutation because they have one X and one Y chromosome) and in females who are homozygous for the gene mutation (see zygosity). Females with one copy of the mutated gene are carriers.

Contents

X-linked inheritance means that the gene causing the trait or the disorder is located on the X chromosome. Females have two X chromosomes while males have one X and one Y chromosome. Expression of X-linked conditions in female carriers can vary greatly due to random X-chromosome inactivation (Lyonization) within each cell. [1] Differences in X-chromosome inactivation (known as skewed X-inactivation) occurs due to some cells expressing one X allele and some the other. Decades of research has led to the consensus that conditions be considered X-linked and that the "dominant" and "recessive" designations be retired. [2]

The current estimate of sequenced X-linked genes is 499, and the total, including vaguely defined traits, is 983. [3]

Patterns of inheritance

Patterns of X-linked recessive inheritance in a royal family Haemophilia family tree.GIF
Patterns of X-linked recessive inheritance in a royal family

In humans, inheritance of X-linked recessive traits follows a unique pattern made up of three points.

Pushback on recessive/dominant terminology

A few scholars have suggested discontinuing the use of the terms dominant and recessive when referring to X-linked inheritance. [7] The possession of two X chromosomes in females leads to dosage issues which are alleviated by X-inactivation. [8] Stating that the highly variable penetrance of X-linked traits in females as a result of mechanisms such as skewed X-inactivation or somatic mosaicism is difficult to reconcile with standard definitions of dominance and recessiveness, scholars have suggested referring to traits on the X chromosome simply as X-linked. [7]

Examples

Most common

The most common X-linked recessive disorders are: [9]

Less common disorders

Theoretically, a mutation in any of the genes on chromosome X may cause disease, but below are some notable ones, with short description of symptoms:

See also

References

  1. Dobyns, William B. (April 2006). "The pattern of inheritance of X-linked traits is not dominant or recessive, just X-linked". Acta Paediatrica (Oslo, Norway: 1992). Supplement. 95 (451): 11–15. doi:10.1111/j.1651-2227.2006.tb02383.x. ISSN   0803-5326. PMID   16720459.
  2. Basava, Sanjana; Billington, Charles J.; Carrel, Laura; Biesecker, Leslie G.; Dobyns, William B. (July 2025). "Patterns of X-linked inheritance: A new approach for the genome era". Genetics in Medicine: Official Journal of the American College of Medical Genetics. 27 (7): 101384. doi:10.1016/j.gim.2025.101384. ISSN   1530-0366. PMID   39963886.{{cite journal}}: CS1 maint: article number as page number (link)
  3. "OMIM X-linked Genes". nih.gov. Archived from the original on 7 March 2016. Retrieved 3 May 2018.
  4. "Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals". National Center for Biotechnology Information. 8 July 2009. Retrieved 9 June 2020.
  5. "History of Bleeding Disorders". National Hemophilia Foundation. 2014-03-04. Retrieved 2020-06-09.
  6. Pierce, Benjamin A. (2020). Genetics: A Conceptual Approach. Macmillan Learning. pp. 154–155. ISBN   978-1-319-29714-5.
  7. 1 2 Dobyns, William B.; Filauro, Allison; Tomson, Brett N.; Chan, April S.; Ho, Allen W.; Ting, Nicholas T.; Oosterwijk, Jan C.; Ober, Carole (2004). "Inheritance of most X-linked traits is not dominant or recessive, just X-linked". American Journal of Medical Genetics. 129A (2): 136–43. doi:10.1002/ajmg.a.30123. PMID   15316978. S2CID   42108591.
  8. Shvetsova, Ekaterina; Sofronova, Alina; Monajemi, Ramin; Gagalova, Kristina; Draisma, Harmen H. M.; White, Stefan J.; Santen, Gijs W. E.; Chuva de Sousa Lopes, Susana M.; Heijmans, Bastiaan T.; van Meurs, Joyce; Jansen, Rick (March 2019). "Skewed X-inactivation is common in the general female population". European Journal of Human Genetics. 27 (3): 455–465. doi: 10.1038/s41431-018-0291-3 . ISSN   1476-5438. PMC   6460563 . PMID   30552425.
  9. GP Notebook - X-linked recessive disorders Archived 2011-06-13 at the Wayback Machine Retrieved on 5 Mars, 2009
  10. "OMIM Color Blindness, Deutan Series; CBD". nih.gov. Archived from the original on 29 September 2009. Retrieved 3 May 2018.
  11. Michael Price (8 October 2009). "Case Closed: Famous Royals Suffered From Hemophilia". ScienceNOW Daily News. AAAS. Archived from the original on 20 October 2013. Retrieved 9 October 2009.
  12. Rogaev, Evgeny I.; Grigorenko, Anastasia P.; Faskhutdinova, Gulnaz; Kittler, Ellen L. W.; Moliaka, Yuri K. (2009). "Genotype Analysis Identifies the Cause of the 'Royal Disease'". Science. 326 (5954): 817. Bibcode:2009Sci...326..817R. doi: 10.1126/science.1180660 . PMID   19815722. S2CID   206522975.
  13. "Hemophilia B". Archived 2007-12-01 at the Wayback Machine National Hemophilia Foundation.
  14. Carlo Gelmetti; Caputo, Ruggero (2002). Pediatric Dermatology and Dermatopathology: A Concise Atlas. T&F STM. p. 160. ISBN   1-84184-120-X.
  15. "X-linked Agammaglobulinemia: Immunodeficiency Disorders: Merck Manual Professional". Archived from the original on 2008-02-18. Retrieved 2008-03-01.
  16. "Diseases Treated at St. Jude". stjude.org. Archived from the original on 15 August 2007. Retrieved 3 May 2018.
  17. "Favism - Doctor". patient.info. Archived from the original on 21 November 2017. Retrieved 3 May 2018.

[Female X-linked disorders]