Editing X-inactivation (section)

==Uses in experimental biology==
[[Stanley Michael Gartler]] used X-chromosome inactivation to demonstrate the clonal origin of cancers. Examining normal tissues and tumors from females heterozygous for isoenzymes of the sex-linked [[glucose-6-phosphate dehydrogenase|G6PD]] gene demonstrated that tumor cells from such individuals express only one form of G6PD, whereas normal tissues are composed of a nearly equal mixture of cells expressing the two different phenotypes. This pattern suggests that a single cell, and not a population, grows into a cancer.<ref>{{cite journal | vauthors = Linder D, Gartler SM | title = Glucose-6-phosphate dehydrogenase mosaicism: utilization as a cell marker in the study of leiomyomas | journal = Science | volume = 150 | issue = 3692 | pages = 67–9 | date = October 1965 | pmid = 5833538 | doi = 10.1126/science.150.3692.67 | bibcode = 1965Sci...150...67L | s2cid = 33941451 }}</ref> However, this pattern has been proven wrong for many cancer types, suggesting that some cancers may be polyclonal in origin.<ref>{{cite journal | vauthors = Parsons BL | title = Many different tumor types have polyclonal tumor origin: evidence and implications | journal = Mutation Research | volume = 659 | issue = 3 | pages = 232–47 | year = 2008 | pmid = 18614394 | doi = 10.1016/j.mrrev.2008.05.004 | bibcode = 2008MRRMR.659..232P | url = https://zenodo.org/record/1259237 }}</ref>

Besides, measuring the methylation (inactivation) status of the polymorphic human androgen receptor (HUMARA) located on X-chromosome is considered the most accurate method to assess clonality in female cancer biopsies.<ref>{{cite journal | vauthors = Chen GL, Prchal JT | title = X-linked clonality testing: interpretation and limitations | journal = Blood | volume = 110 | issue = 5 | pages = 1411–9 | date = September 2007 | pmid = 17435115 | pmc = 1975831 | doi = 10.1182/blood-2006-09-018655 }}</ref> A great variety of tumors was tested by this method, some, such as renal cell carcinoma,<ref>{{cite journal | vauthors = Petersson F, Branzovsky J, Martinek P, Korabecna M, Kruslin B, Hora M, Peckova K, Bauleth K, Pivovarcikova K, Michal M, Svajdler M, Sperga M, Bulimbasic S, Leroy X, Rychly B, Trivunic S, Kokoskova B, Rotterova P, Podhola M, Suster S, Hes O | display-authors = 6 | title = The leiomyomatous stroma in renal cell carcinomas is polyclonal and not part of the neoplastic process | journal = Virchows Archiv | volume = 465 | issue = 1 | pages = 89–96 | date = July 2014 | pmid = 24838683 | doi = 10.1007/s00428-014-1591-9 | s2cid = 24870232 }}</ref> found monoclonal while others (e.g. mesothelioma<ref>{{cite journal | vauthors = Comertpay S, Pastorino S, Tanji M, Mezzapelle R, Strianese O, Napolitano A, Baumann F, Weigel T, Friedberg J, Sugarbaker P, Krausz T, Wang E, Powers A, Gaudino G, Kanodia S, Pass HI, Parsons BL, Yang H, Carbone M | title = Evaluation of clonal origin of malignant mesothelioma | journal = Journal of Translational Medicine | volume = 12 | pages = 301 | date = December 2014 | pmid = 25471750 | pmc = 4255423 | doi = 10.1186/s12967-014-0301-3 | doi-access = free }}</ref>) were reported polyclonal.

Researchers have also investigated using X-chromosome inactivation to silence the activity of autosomal chromosomes. For example, Jiang ''et al.'' inserted a copy of the Xist gene into one copy of chromosome 21 in [[IPS cell|stem cells]] derived from an individual with trisomy 21 ([[Down syndrome]]).<ref>{{cite journal | vauthors = Jiang J, Jing Y, Cost GJ, Chiang JC, Kolpa HJ, Cotton AM, Carone DM, Carone BR, Shivak DA, Guschin DY, Pearl JR, Rebar EJ, Byron M, Gregory PD, Brown CJ, Urnov FD, Hall LL, Lawrence JB | display-authors = 6 | title = Translating dosage compensation to trisomy 21 | journal = Nature | volume = 500 | issue = 7462 | pages = 296–300 | date = August 2013 | pmid = 23863942 | pmc = 3848249 | doi = 10.1038/nature12394 | bibcode = 2013Natur.500..296J }}</ref> The inserted Xist gene induces Barr body formation, triggers stable heterochromatin modifications, and silences most of the genes on the extra copy of chromosome 21. In these modified stem cells, the Xist-mediated gene silencing seems to reverse some of the defects associated with Down syndrome.