ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2019-1-164-174ssmu-2181Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSРаспределение длины теломер на отдельных плечах индивидуальных хромосом при бронхиальной астмеTelomere length distribution on individual chromosome arms in patients with bronchial asthmahttps://orcid.org/0000-0001-5748-9116БарковскаяМ. Ш.BarkovskayaM. Sh.

Барковская Маргарита Шамилевна, младший научный сотрудник, лаборатория клинической иммунопатологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Barkovskaya Margarita Sh., Junior Researcher, Laboratory of Clinical Immunopathology

14, Yadrintsevskaya Str., Novosibirsk, 630099

margaritabarkovskaya@gmail.comhttps://orcid.org/0000-0003-3327-3630БлиноваЕ. А.BlinovaE. A.

Блинова Елена Андреевна, кандидат биологических наук, старший научный сотрудник, лаборатория клинической иммунопатологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Blinova Elena A., PhD, Senior Researcher, Laboratory of Clinical Immunopathology

14, Yadrintsevskaya Str., Novosibirsk, 630099

КоняхинаЮ. В.KonyahinaJ. V.

Коняхина Юлия Владимировна, клинический ординатор

630099, г. Новосибирск, ул. Ядринцевская, 14

Konyahina Julia V., Resident Physician

14, Yadrintsevskaya Str., Novosibirsk, 630099

ЛеоноваМ. И.LeonovaM. I.

Леонова Марина Ивановна, врач аллерголог-иммунолог, отделение аллергологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Leonova Marina I., Allergist-immunologist, Department of Allegology

14, Yadrintsevskaya Str., Novosibirsk, 630099

НепомнящихВ. М.NepomniashchikchV. M.

Непомнящих Вера Макаровна, врач аллерголог-иммунолог, отделение аллергологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Nepomniashchikch Vera M., Allergist-immunologist, Department of Allegology

14, Yadrintsevskaya Str., Novosibirsk, 630099

ДеминаД. В.DeminaD. V.

Демина Дарья Владимировна, кандидат медицинских наук, врач аллерголог-иммунолог, заведующая отделением аллергологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Demina Darja V., PhD, Allergist-immunologist, Head of the Department of Allegology

14, Yadrintsevskaya Str., Novosibirsk, 630099

КожевниковВ. С.KozhevnikovV. S.

Кожевников Владимир Сергеевич, доктор медицинских наук, профессор, главный научный сотрудник, лаборатория клинической иммунопатологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Kozhevnikov Vladimir S., DM, Professor, Chief Researcher of Laboratory of Clinical Immunopathology

14, Yadrintsevskaya Str., Novosibirsk, 630099

https://orcid.org/0000-0002-1756-1782КозловВ. А.KozlovV. A.

Козлов Владимир Александрович, доктор. медицинских наук, профессор, академик РАН, научный руководитель, заведующий лабораторией клинической иммунопатологии, НИИФКИ

630099, г. Новосибирск, ул. Ядринцевская, 14

Kozlov Vladimir A., DM, Professor, Аcademician of RAS, Scientific Supervisor of RIFCI, Head of the Laboratory of Clinical Immunopathology, RIFCI

14, Yadrintsevskaya Str., Novosibirsk, 630099

Научно-исследовательский институт фундаментальной и клинической иммунологии (НИИФКИ)РоссияResearch Institute of Fundamental and Clinical Immunology (RIFCI)Russian Federation201916052019181164174Copyright © Барковская М.Ш., Блинова Е.А., Коняхина Ю.В., Леонова М.И., Непомнящих В.М., Демина Д.В., Кожевников В.С., Козлов В.А., 20192019Барковская М.Ш., Блинова Е.А., Коняхина Ю.В., Леонова М.И., Непомнящих В.М., Демина Д.В., Кожевников В.С., Козлов В.А.Barkovskaya M.S., Blinova E.A., Konyahina J.V., Leonova M.I., Nepomniashchikch V.M., Demina D.V., Kozhevnikov V.S., Kozlov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/2181Цель

Цель.Охарактеризовать длину теломерных последовательностей на отдельных плечах индивидуальных хромосом у больных бронхиальной астмой (БА).

Материалы и методы

Материалы и методы. Были использованы метафазные пластинки, полученные из мононуклеарной фракции периферической крови пациентов с БА (n = 10, средний возраст (44 ± 8,2) года) и условноздоровых доноров (n = 10, средний возраст (44 ± 8,4) года). Для измерения длины теломер на отдельных плечах индивидуальных хромосом использовали количественную флуоресцентную гибридизацию in situ. Новое программное обеспечение (MeTeLen, http://www.bionet.nsc.ru/en/development/application-development/development-of-a-computer/metelen.html) применялось для оценки количества теломерных повторов на изображениях метафазных хромосом.

Результаты

Результаты. Показано, что теломерные последовательности на отдельных плечах ряда индивидуальных хромосом (4q, 5q, 9p, 10q, 11p, 13p, 15q, 18q, 19q) у пациентов с БА укорочены по сравнению с длиной теломер у доноров (p < 0,05; критерий Манна – Уитни). Также для исследуемых групп были определены теломерные последовательности, укороченные и удлиненные относительно средней длины теломер по группе (p < 0,05; критерий Вилкоксона). Были обнаружены следующие различия и сходства между теломерными профилями пациентов и доноров: у пациентов теломерные последовательности 4p, 6q, 8p были удлинены, а 2q, 9q, 11p, 15 q – укорочены относительно средней длины теломер. При этом длина данных теломерных последовательностей не отличалась от средней длины теломер в группе доноров. Вместе с тем в обеих группах теломерные последовательности 12p, 16p, 17p, 19p были короче, а 3p – длиннее, чем средняя длина теломер.

Заключение

Заключение. Таким образом, обнаружено уменьшение длины теломер на отдельных плечах индивидуальных хромосом у пациентов с БА в сравнении с донорами, а также выявлены особенности распределения длины теломерных последовательностей при данной патологии. Мы полагаем, что механизмы изменения теломерного профиля при БА требуют дальнейшего изучения.

Objective

Objective. The purpose of this study was to evaluate the length of telomeres in the arms of individual chromosomes in patients with bronchial asthma (BA).

Materials and methods

Materials and methods. The study included patients with BA (n = 10, the mean age (44 ± 8.2) years) and healthy donors (n = 10, the mean age (44 ± 8.4) years). Metaphase spreads obtained from peripheral blood mononuclear cells were used. At the time of sampling BA patients received treatment at the Clinic of Immunopathology, Novosibirsk. BA was diagnosed by physicians according to GINA-2016. For measurement of telomere length on individual chromosome arms we used quantitative fluorescent in situ hybridization with a PNA-probe specific for telomeres. We used inverted DAPI banding for chromosome identification (according to ISCN-2013). For each individual 5 metaphase cells were analyzed. We applied the newly developed MeTeLen software to estimate the telomere repeats quantity (http:// www.bionet.nsc.ru/en/development/application-development/development-of-a-computer/metelen.html) in metaphase images. For enhanced image analysis compared with the previously developed programs, we included estimation of background signal and correction of defects of the optical system.

Results

Results. Comparing of telomere length show, that telomeres in the certain chromosome arms (4q, 5q, 9p, 10 q, 11p, 13p, 15q, 18q, 19q) in BA are significantly shorter than in corresponding group of donors (p < 0.05, Mann – Whitney U-test). For both studied groups we also evaluated telomere sequences shortened and elongated relative to the average telomere length in the group (p < 0.05, Wilcoxon-signed-runk test). The following differences and similarities between the telomere profiles of patients and donors were determined: the telomere sequences 4p, 6q, 8p were elongated and 2q, 9q, 11p, 15q were shortened relative to the average telomere length in BA patients. Moreover, this telomere sequences did not differ from the average telomere length in the group of donors. At the same time, the telomere sequences 12p, 16p, 17p, 19p were significantly shorter, and 3p was longer than the average telomere length in both groups.

Conclusions

Conclusions. We guess, that the observed significant shortening of telomere length on individual chromosome arms in BA, as compared to donors, is relevant in pathogenesis of this disorder. The revealed features of telomere profile of patients with BA may be a result of different telomere length maintenance mechanisms and may influence to the development of asthma that needs further study.

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