Экспериментальные подходы к изучению влияния вариантов нуклеотидной последовательности на прохождение сплайсинга в генах с низкой экспрессией в клинически доступных тканях

Варианты нуклеотидной последовательности (ВНП), влияющие на процесс сплайсинга предшественника матричной РНК (пре-мРНК), являются одной из установленных причин развития широкого спектра наследственных заболеваний. Экспериментальное подтверждение событий аберрантного сплайсинга играет важную роль в медицинской генетике при определении патогенности таких вариантов. Однако ключевым ограничением таких исследований часто является низкая экспрессия исследуемого гена в клинически доступных тканях, что делает невозможным прямой РНК-анализ на биоматериале пациента. Настоящая работа систематизирует экспериментальные подходы, разработанные для оценки влияния ВНП на прохождение сплайсинга в условиях недостаточного уровня экспрессии целевого гена. Кроме того, рассматриваются возможности и ограничения каждого метода и их потенциальная роль в определении патогенности вариантов при наследственных заболеваниях.

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