medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2026.06.13-25medgen-3474Research ArticleНАУЧНЫЙ ОБЗОРREVIEWЭкспериментальные подходы к изучению влияния вариантов нуклеотидной последовательности на прохождение сплайсинга в генах с низкой экспрессией в клинически доступных тканяхExperimental approaches to study the effects of nucleotide sequence variants on splicing in low-expression genes in clinically accessible tissuesЛукинаТ. Д.LukinaT. D.

117513, г. Москва, ул. Островитянова, д. 1

1 Ostrovityanova str., Moscow, 117513

СпарберП. А.SparberP. A.

115522, г. Москва, ул. Москворечье, д.1

1 Moskvorechie str., Moscow, 115522

psparber93@gmail.comФГАОУ ВО «Российский Национальный Исследовательский Медицинский Университет им. Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияPirogov Russian National Research Medical UniversityRussian FederationФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Center for Medical GeneticsRussian Federation2026100720262561325Copyright © Лукина Т.Д., Спарбер П.А., 20262026Лукина Т.Д., Спарбер П.А.Lukina T.D., Sparber P.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/3474

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.

Variants affecting pre-mRNA splicing are an established cause of a wide range of hereditary disorders. Experimental validation of aberrant splicing events play an important role in medical genetics in determining the pathogenicity of such variants. However, a key limitation is often the low expression of the target gene in clinically accessible tissues, which makes direct RNA analysis from patient samples impossible. The present work systematizes experimental approaches developed to assess the effects of variants on splicing under conditions of insufficient target gene expression. Furthermore, the possibilities and limitations of each method are discussed, along with their potential role in determining the pathogenicity of variants in hereditary diseases.

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