REVIEW: Methods for Functional Characterization of Genetic Polymorphisms of Non-Coding Regulatory Regions of the Human Genome

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Aksinya N. Uvarova^1,a*, Elena A. Tkachenko^2,3, Ekaterina M. Stasevich^1,4, Elina A. Zheremyan¹, Kirill V. Korneev¹, Dmitry V. Kuprash^1,3

¹Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

²Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

³Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

⁴Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received: November 20, 2023; Revised: March 27, 2024; Accepted: April 11, 2024

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Currently, numerous associations between genetic polymorphisms and various diseases have been characterized through the Genome-Wide Association Studies. Majority of the clinically significant polymorphisms are localized in non-coding regions of the genome. While modern bioinformatic resources make it possible to predict molecular mechanisms that explain influence of the non-coding polymorphisms on gene expression, such hypotheses require experimental verification. This review discusses the methods for elucidating molecular mechanisms underlying dependence of the disease pathogenesis on specific genetic variants within the non-coding sequences. A particular focus is on the methods for identification of transcription factors with binding efficiency dependent on polymorphic variations. Despite remarkable progress in bioinformatic resources enabling prediction of the impact of polymorphisms on the disease pathogenesis, there is still the need for experimental approaches to investigate this issue.

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KEY WORDS: functional polymorphisms, regulatory genomic regions, transcription factors, reporter analysis, CRISPR-Cas

DOI: 10.1134/S0006297924060026

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