References

vavilov

Вавиловский журнал генетики и селекции

Vavilov Journal of Genetics and Breeding

2500-3259

Institute of Cytology and Genetics of Siberian Branch of the RAS

10.18699/VJGB-23-61

vavilov-3867

Research Article

ГЕНЕТИКА ЧЕЛОВЕКА

HUMAN GENETICS

Мозаичная потеря Y-хромосомы при нейродегенеративных и онкологических заболеваниях человека

Mosaic loss of the Y chromosome in human neurodegenerative and oncological diseases

https://orcid.org/0000-0002-7785-734X

Кузнецова

И. Л.

Kuznetsova

I. L.

Москва; Сочи

Moscow; Sochi

irakuzn@gmail.com

https://orcid.org/0000-0002-5565-7961

Уральский

Л. И.

Uralsky

L. I.

Москва; Сочи

Moscow; Sochi

https://orcid.org/0000-0002-0594-0654

Тяжелова

Т. В.

Tyazhelova

T. V.

Москва

Moscow

Андреева

Т. В.

Andreeva

T. V.

Москва; Сочи

Moscow; Sochi

https://orcid.org/0000-0003-0594-4767

Рогаев

Е. И.

Rogaev

E. I.

Москва; Сочи

Moscow; Sochi

Институт общей генетики им. Н.И. Вавилова Российской академии наук, отдел геномики и генетики человека; Научно-технологический университет «Сириус», Научный центр генетики и наук о жизниРоссияVavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human Genetics; Sirius University of Science and Technology, Scientific Center for Genetics and Life SciencesRussian Federation

Институт общей генетики им. Н.И. Вавилова Российской академии наук, отдел геномики и генетики человекаРоссияVavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human GeneticsRussian Federation

Институт общей генетики им. Н.И. Вавилова Российской академии наук, отдел геномики и генетики человека; Научно-технологический университет «Сириус», Научный центр генетики и наук о жизни; Московский государственный университет им. М.В. Ломоносова, Центр генетики и генетических технологий, биологический факультетРоссияVavilov Institute of General Genetics, Russian Academy of Sciences, Department of Genomics and Human Genetics; Sirius University of Science and Technology, Scientific Center for Genetics and Life Sciences Lomonosov Moscow State University, Center for Genetics and Genetic Technologies, Faculty of BiologyRussian Federation

2023

09092023

275502511

2023

Кузнецова И.Л., Уральский Л.И., Тяжелова Т.В., Андреева Т.В., Рогаев Е.И.

Kuznetsova I.L., Uralsky L.I., Tyazhelova T.V., Andreeva T.V., Rogaev E.I.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://vavilov.elpub.ru/jour/article/view/3867

Одно из наиболее актуальных направлений современной генетики и геномики человека – разработка новых биомаркеров для прогнозирования и раннего выявления заболеваний человека, а также для мониторинга ответа на терапию. До недавнего времени считалось, что функция генов Y-хромосомы человека ограничена определением пола и контролем сперматогенеза. Благодаря созданию крупных баз данных, полученных на основе метода поиска ассоциаций (GWAS), произошел переход к использованию больших выборок при анализе генетических изменений в норме и при патологиях, в том числе стало возможно оценить связь мозаичной анеуплоидии по Y-хромосоме в соматических клетках с более короткой продолжительностью жизни у мужчин по сравнению с женщинами. На основе данных Британского биобанка (UK Biobank) была обнаружена ассоциация между мозаичной потерей Y-хромосомы (mLOY) в лейкоцитах периферической крови с возрастом мужчин старше 70 лет, а также с рядом онкологических, сердечных, метаболических, нейродегенеративных и психических заболеваний. В результате mLOY в клетках периферической крови стала рассматриваться в качестве потенциального маркера биологического возраста мужчин и как маркер определенных возрастных болезней. На сегодняшний день определено множество ассоциаций между mLOY и генами, выявленными на основании данных GWAS и транскриптомов в пораженных тканях, однако не установлены ни точная причина возникновения mLOY, ни влияние и последствия этого феномена на уровне всего организма. В частности, неясно, влияет ли анеуплоидия по Y-хромосоме в клетках крови на развитие патологий, проявляющихся в других органах, например на мозг при болезни Альцгеймера, или представляет собой нейтральный биомаркер общей геномной нестабильности. В обзоре рассмотрены основные патологии и генетические факторы, ассоциированные с mLOY, и гипотезы их взаимосвязи. Особое внимание уделено последним исследованиям, посвященным mLOY в клетках мозга при болезни Альцгеймера.

The development of new biomarkers for prediction and early detection of human diseases, as well as for monitoring the response to therapy is one of the most relevant areas of modern human genetics and genomics. Until recently, it was believed that the function of human Y chromosome genes was limited to determining sex and controlling spermatogenesis. Thanks to occurance of large databases of the genome-wide association study (GWAS), there has been a transition to the use of large samples for analyzing genetic changes in both normal and pathological conditions. This has made it possible to assess the association of mosaic aneuploidy of the Y chromosome in somatic cells with a shorter lifespan in men compared to women. Based on data from the UK Biobank, an association was found between mosaic loss of the Y chromosome (mLOY) in peripheral blood leukocytes and the age of men over 70, as well as a number of oncological, cardiac, metabolic, neurodegenerative, and psychiatric diseases. As a result, mLOY in peripheral blood cells has been considered a potential marker of biological age in men and as a marker of certain age-related diseases. Currently, numerous associations have been identified between mLOY and genes based on GWAS and transcriptomes in affected tissues. However, the exact cause of mLOY and the impact and consequences of this phenomenon at the whole organism level have not been established. In particular, it is unclear whether aneuploidy of the Y chromosome in blood cells may affect the development of pathologies that manifest in other organs, such as the brain in Alzheimer’s disease, or whether it is a neutral biomarker of general genomic instability. This review examines the main pathologies and genetic factors associated with mLOY, as well as the hypotheses regarding their interplay. Special attention is given to recent studies on mLOY in brain cells in Alzheimer’s disease.

мозаичная потеря Y-хромосомы (mLOY)болезнь АльцгеймераGWASвозрастные заболеванияонкологические заболевания

mosaic loss of Y chromosome (mLOY)Alzheimer’s diseaseGWASage-related diseasesoncological diseases

The study was supported by Russian Science Foundation, Research Project No. 19-75-30039.

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The authors declare that there are no conflicts of interest present.