X-linked dominant inheritance: Difference between revisions

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''Main Article:'' <u>[[Sex linkage]]</u>{{short description|Mode of inheritance}}

{{refimprove|date=September 2009}}

[[File:X-linked dominant.svg|thumb|upright=1.75|X-linked dominant inheritance]]

'''X-linked dominant inheritance''', sometimes referred to as '''X-linked dominance''', is a mode of [[geneticsGenetics|genetic]] [[Heredity|inheritance]] by which a [[dominant gene]] is carried on the [[X chromosome]]. As an inheritance pattern, it is less common than the [[X-linked recessive inheritance|X-linked recessive]] type. In medicine, X-linked dominant inheritance indicates that a gene responsible for a [[genetic disorder]] is located on the X chromosome, and only one copy of the [[allele]] is sufficient to cause the disorder when inherited from a parent who has the disorder. In this case, someone who [[Gene expression|expresses]] an X-linked dominant allele will exhibit the disorder and be considered affected.{{cn|date=January 2024}} The pattern of inheritance is sometimes called ''criss-cross inheritance''.<ref>{{Cite book |last=Meneely |first=Philip Mark |url=https://www.worldcat.org/title/951645141 |title=Genetics: genes, genomes, and evolution |last2=Dawes Hoang |first2=Rachel |last3=Okeke |first3=Iruka N. |last4=Heston |first4=Katherine |date=2017 |publisher=Oxford University Press |isbn=978-0-19-879536-0 |___location=Oxford |pages=271 |oclc=951645141}}</ref>

X-linked dominant traits do not necessarily affect males more than females (unlike [[X-linked recessive]] traits). The exact pattern of inheritance varies, depending on whether the father or the mother has the trait of interest. All fathers that are affected by an X-linked dominant disorder, will have affected daughters, but not affected sons. However, if the mother is also affected then sons will have a chance of being affected, depending on whether a dominant or recessive X chromosome is passed on. When the son is affected, the mother will always be affected. Some X-linked dominant conditions are embryonic lethal in males, making them appear to only occur in females.<ref>{{Cite journal |last=Wettke-Schäfer |first=Roswitha |last2=Kantner |first2=Gisela |date=July 1983 |title=X-linked dominant inherited diseases with lethality in hemizygous males |url=https://doi.org/10.1007/BF00289472 |journal=Human Genetics |language=en |volume=64 |issue=1 |pages=1–23 |doi=10.1007/BF00289472 |issn=1432-1203|url-access=subscription }}</ref>

Some scholars have suggested discontinuing the terms dominant and recessive when referring to X-linked inheritance due to the multiple mechanisms that can result in the expression of X-linked traits in females, which include cell autonomous expression, skewed X-inactivation, clonal expansion, and somatic mosaicism.<ref name=pmid15316978>{{cite journal | vauthors = Dobyns WB, Filauro A, Tomson BN, Chan AS, Ho AW, Ting NT, Oosterwijk JC, Ober C | title = Inheritance of most X-linked traits is not dominant or recessive, just X-linked | journal = American Journal of Medical Genetics. Part A | volume = 129A | issue = 2 | pages = 136–43 | date = August 2004 | pmid = 15316978 | doi = 10.1002/ajmg.a.30123 }}</ref>

==Genetics==

As the X chromosome is one of the [[sex chromosome]]s (the other being the [[Y chromosome]]), X-linked inheritance is determined by the [[sex]] of the parent carrying a specific gene and can often seem complex. This is due to the fact that, typically, [[female]]s have two copies of the X-chromosome, while [[male]]s have only one copy. The difference between [[Dominance (genetics)#Dominant trait|dominant]] and [[Dominance (genetics)#Recessive|recessive]] inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.{{fact|date=January 2018}}

As the X chromosome is one of the [[sex chromosome]]s (the other being the [[Y chromosome]]), X-linked

inheritance is determined by the [[sex]] of the parent carrying a specific gene and can often seem complex. This is due to the fact that, typically, [[female]]s have two copies of the X-chromosome, while [[male]]s have only one copy. The difference between [[Dominance (genetics)#Dominant trait|dominant]] and [[Dominance (genetics)#Recessive|recessive]] inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.{{fact|date=January 2018}}

Males can only get an X-linked chromosomedominant fromdisorders theirtend motherto whilstaffect females getmore anoften Xbecause chromosome from both parents. As a result, femalesthey tend to showbe higherdevelopmentally prevalencefatal ofin X-linkedmales. dominantThis disordersis because theymales have moreonly ofone acopy chanceof toX-chromosome inheritwhile afemales faultyhave Xtwo chromosomecopies.{{fact|date=January 2018}}

===Inheritance===

{| class=wikitable border=1 cellpadding=2 cellspacing=0 align=right width=400

|-

| align=center valign=center |[[Image:Xlink dominant mother.jpg|thumb|175px]] || align=center valign=center |[[Image:X-link dominant father.jpg|thumb|175px]]

|-

| align=center colspan=2 valign=top|<small>X-linked dominant inheritance works differently depending upon whether the mother (left image) or father (right image) is the carrier of a gene that causes a disease or disorder.</small>

|-

|}

In X-linked dominant inheritance, when the mother alone is the [[genetic carrier|carrier]] of a mutated, or defective gene associated with a disease or disorder; she herself will have the disorder. Her children will inherit the disorder as follows:

* Of her daughters and sons: 50% will have the disorder, 50% will be completely unaffected. Children of either sex have an even chance of receiving either of their mother's two X chromosomes, one of which contains the defective gene in question.

*Of her daughters and sons: 50% will have the disorder, 50% will be completely unaffected. Children of either sex have an even chance of receiving either of their mother's two X chromosomes, one of which contains the defective gene in question.

When the father alone is the carrier of a defective gene associated with a disease or disorder, he too will have the disorder. His children will inherit the disorder as follows:

* Of theirhis daughters: 100% will have the disorder, since all of thehis daughters will receive aone copy of theirhis father'ssingle X chromosome.

* Of his daughterssons: 100%none will have the disorder,; sincesons alldo of his daughters willnot receive onean copyX ofchromosome hisfrom singletheir X chromosomefather.

*Of his sons: none will have the disorder; sons do not receive an X chromosome from their father.

If both parents were carriers of a defective gene associated with a disease or disorder, they would both have the disorder. Their children would inherit the disorder as follows:

* Of their daughters: 100% will have the disorder, since all of the daughters will receive a copy of their father's X chromosome.

* Of the sons: 50% will have the disorder, 50% will be completely unaffected. Sons have an equal chance of receiving either of their mother's X chromosomes.

In such a case, where both parents carry and thus are affected by an X-linked dominant disorder, the chance of a daughter receiving two copies of the X chromosome with the defective gene is 50%, since daughters receive one copy of the X chromosome from both parents. Were this to occur with an X-linked dominant disorder, that daughter would likely experience a more severe form.

*Of their daughters: 100% will have the disorder, since all of the daughters will receive a copy of their father's X chromosome.

*Of the sons: 50% will have the disorder, 50% will be completely unaffected. Sons have an equal chance of receiving either of their mother's X chromosomes.

Some X-linked dominant conditions such as [[Aicardi Syndromesyndrome]] are fatal to boys,; therefore only girls with these conditions survive, or boys with [[Klinefelter's syndrome]] (and hence have more than one X chromosome).

In such a case, where both parents carry and thus are affected by an X-linked dominant disorder, the chance of a daughter receiving two copies of the X chromosome with the defective gene is 50%, since daughters receive one copy of the X chromosome from both parents. Were this to occur with an X-linked dominant disorder, that daughter would likely experience a more severe form.

SomeA few scholars have suggested discontinuing the use of the terms ''dominant'' and ''recessive'' when referring to X-linked inheritance, duestating tothat the multiplehighly mechanisms that can result in thevariable expressionpenetrance of X-linked traits in females, whichas includea cellresult autonomousof expression,mechanisms such as [[skewed X-inactivation,]] clonalor expansion,[[somatic mosaicism]] is difficult to andreconcile somaticwith mosaicismstandard definitions of dominance and recessiveness.<ref name="pmid15316978">{{cite journal | vauthors = Dobyns WB, Filauro A, Tomson BN, Chan AS, Ho AW, Ting NT, Oosterwijk JC, Ober C |date=August 2004|title = Inheritance of most X-linked traits is not dominant or recessive, just X-linked | journal = American Journal of Medical Genetics. Part A | volume = 129A | issue = 2 | pages = 136–43 | date = August 2004 | pmid = 15316978 | doi = 10.1002/ajmg.a.30123 |pmid=15316978}}</ref>

Some X-linked dominant conditions such as [[Aicardi Syndrome]] are fatal to boys, therefore only girls with these conditions survive, or boys with [[Klinefelter's syndrome]] (and hence have more than one X chromosome).

==List of dominant X-linked diseases==

* [[Vitamin D]] resistant [[rickets]]: [[X-linked hypophosphatemia]]

* [[Rett syndrome]] (95% of cases are due to sporadic mutations(not inherited))

* [[Fragile -X syndrome]]

* Most cases of [[Alport syndrome]]<ref name=pmid14514738>{{cite journal | vauthors = Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schröder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC | display-authors = 6 | title = X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study | journal = Journal of the American Society of Nephrology | volume = 14 | issue = 10 | pages = 2603–10 | date = October 2003 | pmid = 14514738 | doi = 10.1097/01.ASN.0000090034.71205.74 | doi-access = free | hdl = 2078.1/40773 | hdl-access = free }}</ref>

* [[Incontinentia pigmenti]]<ref>{{cite web | url = http://dermnetnz.org/systemic/incontinentia-pigmenti.html | title = Incontinentia pigmenti | first = Vanessa | last = Ngan | name-list-formatstyle = vanc | publisher = DermNet NZ | date = 2005 }}</ref><ref>{{EMedicine|article|1114205|Incontinentia Pigmenti}}</ref>

* [[Giuffrè–Tsukahara syndrome]]<ref name=pmid20635354>{{cite journal | vauthors = Dalal AB, Sarkar A, Priya TP, Nandineni MR | title = Giuffrè-Tsukahara syndrome: Evidence for X-linked dominant inheritance and review | journal = American Journal of Medical Genetics. Part A | volume = 152A | issue = 8 | pages = 2057–60 | date = August 2010 | pmid = 20635354 | doi = 10.1002/ajmg.a.33505 }}</ref>

* [[Goltz syndrome]]

* X-linked dominant [[porphyria]]<ref name=pmid24131146>{{cite journal | vauthors = Seager MJ, Whatley SD, Anstey AV, Millard TP | title = X-linked dominant protoporphyria: a new porphyria | journal = Clinical and Experimental Dermatology | volume = 39 | issue = 1 | pages = 35–7 | date = January 2014 | pmid = 24131146 | doi = 10.1111/ced.12202 }}</ref>

*[[Fragile X syndrome]]

* [[RettAicardi syndrome]]

== See also ==

* [[Sex linkage]]

*[[X-linked hypophosphatemia]]

* [[X-linked recessive inheritance]]

*[[Rett syndrome]]

*[[Sex linkage]]

*[[Incontinentia pigmenti]]<ref>{{EMedicine|article|1114205|Incontinentia Pigmenti}}</ref>

*[[X-linked recessive inheritance]]

== References ==