Telomerase reverse transcriptase (TERT) plays a crucial role in synthesizing telomeric repeats that safeguard chromosomes from damage and fusion, thereby maintaining genome stability. Mutations in the TERT gene can lead to a deviation in gene expression, impaired enzyme activity, and, as a result, abnormal telomere shortening. Genetic markers of productivity traits in livestock can be developed based on the TERT gene polymorphism for use in marker-associated selection (MAS). In this study, a bioinformatic-based approach is proposed to evaluate the effect of missense single-nucleotide polymorphisms (SNPs) in the pig TERT gene on enzyme function and structure, with the prospect of developing genetic markers.
A comparative analysis of the coding and amino acid sequences of the pig TERT was performed with corresponding sequences of other species. The distribution of polymorphisms in the pig TERT gene, with respect to the enzyme’s structural-functional domains, was established. A three-dimensional model of the pig TERT structure was obtained through homological modeling. The potential impact of each of the 23 missense SNPs in the pig TERTgene on telomerase function and stability was assessed using predictive bioinformatic tools utilizing data on the amino acid sequence and structure of pig TERT.
According to bioinformatic analysis of 23 missense SNPs of the pig TERT gene, a predictive effect of rs789641834 (TEN domain), rs706045634 (TEN domain), rs325294961 (TRBD domain) and rs705602819 (RTD domain) on the structural and functional parameters of the enzyme was established. These SNPs hold the potential to serve as genetic markers of productivity traits. Therefore, the possibility of their application in MAS should be further evaluated in associative analysis studies.
Telomerase reverse transcriptase (TERT) plays a key role in maintaining telomere length and, as a result, genome stability in various eukaryotic species. The study employs a comprehensive approach that combines phylogenetic and bioinformatic analysis with molecular-genetic research methods. The research involved the screening of genetic databases to investigate TERT gene orthologues across organisms belonging to different systematic groups. The TERT gene, which is prevalent in a wide range of eukaryotic biological species, exhibits polymorphisms that have the potential to influence TERT enzyme function and, consequently, animal phenotypes. The primary focus of this study centers on the pig TERT gene, selected as a model organism due to its genetic similarity to humans and its importance as a productive agricultural species. The study explores the exon-intron structure of the TERT gene, analyzing the size of the corresponding transcript and protein product. Furthermore, it provides data on polymorphisms in the pig TERT gene, including missense and synonymous variants. The chromosomal localization of these polymorphisms is characterized and correlated with the domain structure of the TERT enzyme. For the evaluation of the impact of polymorphisms on the structural and functional properties of the TERT enzyme, a molecular-genetic system based on the PCR-RFLP method has been developed. This PCR-RFLP system serves as a basis for subsequent experimental analyses of missense and synonymous variants in population and association studies, allowing for an assessment of the prevalence of these polymorphisms and their significance for animal phenotypes. Given the significance of further laboratory investigation of the pig TERT gene, the developed PCR-RFLP system becomes necessary for the assessment of the functional implications of the polymorphisms within this gene and the potential identification of causative ones among them. The synergy of bioinformatics and molecular-genetic methods in this study lays the groundwork for future impactful research in this field. The presented study holds promise for marker-associated selection, as it opens the way for the use of the TERT gene as a marker in the genetic improvement of agricultural animal species (Saienko et al., 2023).
Saienko, A., Peka, M., Tsereniuk, O., Babicz, M., Kropiwiec-Domańska, K., Onyshchenko, A., Vashchenko, P., & Balatsky, V. (2023). Analysis of polymorphism and development of a molecular-genetic system for genotyping by the telomerase reverse transcriptase (TERT) gene. Biosystems Diversity, 31(4), 436–443. CrossRef
Peka, M., Balatsky, V., Saienko, A., & Tsereniuk, O. (2023). Bioinformatic analysis of the effect of SNPs in the pig TERT gene on the structural and functional characteristics of the enzyme to develop new genetic markers of productivity traits. BMC genomics, 24(1), 487. CrossRef
Саєнко, А. М., Балацький, В. М., Будаква, Є. О., Пека, М. Ю., & Корінний, С. М. (2022). ДНК-типування свиней за геном теломеразної зворотньої транскриптази (TERT). Розведення і генетика тварин, 64, 128-134. CrossRef
Saienko, A. M., Peka, M. Yu., & Balatsky, V. N. (2022, August 30-31). Optimization of the DNA typing technique for TERT and MT2A candidate genes for marker-associated selection of pigs. Forecasts and prospects of scientific discoveries in agricultural sciences and food, Riga, Latvia. CrossRef
Саєнко, А. М., Будаква, Є. О., & Пека, М. Ю. (2022, травень 19). ДНК-типування свиней за геном теломеразної зворотньої транскриптази (TERT). ХX Всеукраїнська науково-практична конференція молодих вчених, Львів, Україна. CrossRef