Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute12057910.23868/gc120579ArticlesСтатьиReview ArticleThe phenomenon of X chromosome inactivation and human diseasesФЕНОМЕН ИНАКТИВАЦИИ Х-ХРОМОСОМЫ И ЗАБОЛЕВАНИЯ ЧЕЛОВЕКАShevchenkoA. IШевченкоА. Иepigene@bionet.nsc.ruFederal Research Center Institute of Cytology and Genetics, the Siberian Branch of the Russian Academy of SciencesФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики СО РАН»Institute of Chemical Biology and Fundamental Medicine, the Siberian Branch of the Russian Academy of SciencesФГБНУ «Институт химической биологии и фундаментальной медицины СО РАН»State Research Institute of Circulation Pathology, Ministry of Healthcare of the Russian FederationФГБУ «Новосибирский научно-исследовательский институт патологии кровообращения имени академика Е.Н. Мешалкина» Министерства здравоохранения РФ15062016112VOL 11, NO2 (2016)ТОМ 11, №2 (2016)616905012023Copyright ©; 2016, Eco-VectorCopyright ©; 2016, Эко-Вектор2016Eco-VectorЭко-Векторhttps://genescells.ru/2313-1829/article/view/120579

In early development, one of the two X chromosomes is randomly inactivated in each somatic cell of female embryos. As a result, women are mosaics that means about a half of their cells bear the active X chromosome inherited from the father, while the genes of the maternally inherited X chromosome are expressed in the other half. Disturbance in the inactivation process during embryogenesis leads to fetal death. Reactivation of the inactive X chromosome in female cells can cause a number of diseases, including cancer and autoimmune disorders. Changes in randomness of X-chromosome inactivation and skewed choice of one of the X-chromosomes for inactivation can influence clinical manifestations of about 400 diseases associated with mutations in X-linked genes. The phenomenon of X chromosome inactivation is also an important issue for successful application of human pluripotent stem cells in biomedical research and regenerative medicine.

На ранней стадии развития у эмбрионов женского пола в каждой соматической клетке случайным образом инактивируется одна из двух Х-хромосом. В результате инактивации формируется мозаичный организм, приблизительно в половине клеток которого активна Х-хромосома, унаследованная от отца, тогда как в оставшейся половине экспрессируются гены Х-хромосомы, полученной от матери. Нарушение процесса инактивации в эмбриогенезе приводит к гибели плода. Реактивация неактивной Х-хромосомы в клетках женщин является причиной развития ряда заболеваний, включая онкологические и аутоиммунные. Изменения случайного характера инактивации Х-хромосомы и предпочтительный выбор для инактивации одной из них способны оказывать влияние на клинические проявления около 400 заболеваний, связанных с мутациями X-сцепленных генов. Феномен инактивации Х-хромосомы необходимо учитывать при работе с плюрипотентными стволовыми клетками человека для их успешного применения в биомедицинских исследованиях и использования для целей регенеративной медицины.

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