Транскрипционные биомаркеры в диагностике генетических заболеваний: возможности, проблемы и перспективы применения

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Аннотация

Количественный анализ транскрипции генов широко применяется в различных областях биологии, а в медицине – используется для диагностики и получения транскриптомного профиля заболеваний (транскриптомного профилирования). В последнее время большой популярностью пользуются методы исследования транскриптомов с применением масштабного секвенирования нового поколения. Транскриптомные исследования позволяют устанавливать, какие клеточные процессы активны в тот или иной момент времени, выявлять динамику транскриптома в различных тканях или состояниях, например во время онтогенеза или при физиологической адаптации, а также выявлять дифференциально экспрессирующиеся гены в случае заболевания. Выраженное изменение уровня транскрипции одного или нескольких генов при патологическом состоянии может быть достаточным для диагностики, то есть может служить транскрипционным биомаркером заболевания. Однако в ряде случаев изменение уровня транскрипции может быть индикатором мутаций, в том числе ведущих к нарушению сплайсинга, транскрипционной активности мобильных элементов и псевдогенов. В обзоре рассмотрены случаи, в которых уровень транскрипции может оказаться полезным для выяснения генетических причин заболевания, а также обсуждены проблемы, которые следует учитывать при использовании транскрипции в качестве диагностического маркера. В перспективе можно ожидать, что специализированные таргетные панели, основанные на анализе транскрипции, будут использоваться не только в качестве диагностического и прогностического инструмента, но и в качестве предиктора структурных нарушений генома, что будет способствовать разработке новых стратегий эффективного лечения заболеваний.

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Л. Н. Нефедова

Московский государственный университет имени М.В. Ломоносова

Автор, ответственный за переписку.
Email: nefedova@mail.bio.msu.ru

биологический факультет

 

Россия, 119991 Москва

Т. Н. Краснова

Московский государственный университет имени М.В. Ломоносова

Email: nefedova@mail.bio.msu.ru

факультет фундаментальной медицины

Россия, 119991 Москва

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2. Рис. 1. Средовые и молекулярно-генетические механизмы, которые могут влиять на уровни транскрипции генов. Условные обозначения: LOF – потеря функции; GOF – усиление функции; NMD – нонсенс-опосредованная деградация мРНК; ТФ – фактор транскрипции; МЭ – мобильный элемент

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3. Рис. 2. Алгоритм разработки таргетной панели на основе транскрипции генов для диагностики заболевания и предсказания специфических структурных изменений в геноме

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