Editing Sex-determination system (section)

==== Y-centered sex determination ====

Some species (including humans) have a gene [[SRY]] on the Y chromosome that determines [[male]]ness. Members of SRY-reliant species can have uncommon XY chromosomal combinations such as [[Klinefelter syndrome|XXY]] and still live.<ref name="Hake-2008">{{cite journal |vauthors=Hake L |title=Genetic Mechanisms of Sex Determination |journal=Nature Education |year=2008 |volume=1 |issue=1 |url=http://www.nature.com/scitable/topicpage/genetic-mechanisms-of-sex-determination-314 |access-date=8 December 2011 |archive-date=19 August 2017 |archive-url=https://web.archive.org/web/20170819121941/http://www.nature.com/scitable/topicpage/genetic-mechanisms-of-sex-determination-314 |url-status=live }}</ref>
Human sex is determined by the presence or absence of a Y chromosome with a functional SRY gene. Once the SRY gene is activated, cells create [[testosterone]] and [[anti-müllerian hormone]] which typically ensures the development of a single, male reproductive system.<ref name="Hake-2008"/> In typical XX embryos, cells secrete [[estrogen]], which drives the body toward the female pathway.

In Y-centered sex determination, the SRY gene is the main gene in determining male characteristics, but multiple genes are required to develop testes. In XY mice, lack of the gene [[DAX1]] on the X chromosome results in sterility, but in humans it causes [[adrenal hypoplasia congenita]].<ref name="Goodfellow-1999">{{cite journal | vauthors = Goodfellow PN, Camerino G | title = DAX-1, an 'antitestis' gene | journal = Cellular and Molecular Life Sciences | volume = 55 | issue = 6–7 | pages = 857–863 | date = June 1999 | pmid = 10412368 | doi = 10.1007/PL00013201 | s2cid = 19764423 | pmc = 11147076 }}</ref> However, when an extra DAX1 gene is placed on the X chromosome, the result is a female, despite the existence of SRY, since it overrides the effects of SRY.<ref name="Chandra-1999">{{cite journal |author=Chandra, H. S. |title=Another way of looking at the enigma of sex determination in Ellobius lutescens |journal=Current Science |date=25 April 1999 |page=1072 |volume=76 |issue=8}}</ref> Even when there are normal sex chromosomes in XX females, duplication or expression of [[SOX9]] causes testes to develop.<ref name="Cox-2011">{{cite journal | vauthors = Cox JJ, Willatt L, Homfray T, Woods CG | title = A SOX9 duplication and familial 46,XX developmental testicular disorder | journal = The New England Journal of Medicine | volume = 364 | issue = 1 | pages = 91–93 | date = January 2011 | pmid = 21208124 | doi = 10.1056/NEJMc1010311 | doi-access = free }}</ref><ref name="Huang-1999">{{cite journal | vauthors = Huang B, Wang S, Ning Y, Lamb AN, Bartley J | title = Autosomal XX sex reversal caused by duplication of SOX9 | journal = American Journal of Medical Genetics | volume = 87 | issue = 4 | pages = 349–353 | date = December 1999 | pmid = 10588843 | doi = 10.1002/(SICI)1096-8628(19991203)87:4<349::AID-AJMG13>3.0.CO;2-N }}</ref> Gradual [[sex reversal]] in developed mice can also occur when the gene [[FOXL2]] is removed from females.<ref name="Uhlenhaut-2009">{{cite journal | vauthors = Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, Riethmacher D, Schütz G, Cooney AJ, Lovell-Badge R, Treier M | display-authors = 6 | title = Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation | journal = Cell | volume = 139 | issue = 6 | pages = 1130–1142 | date = December 2009 | pmid = 20005806 | doi = 10.1016/j.cell.2009.11.021 | doi-access = free }}</ref> Even though the gene [[DMRT1]] is used by birds as their sex locus, species who have XY chromosomes also rely upon DMRT1, contained on chromosome 9, for sexual differentiation at some point in their formation.<ref name="Hake-2008"/>