Ignatieva E V, Yudin N S, Larkin D M
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2023 Jun;27(3):283-292. doi: 10.18699/VJGB-23-34.
Telomeres are the terminal regions of chromosomes that ensure their stability while cell division. Telomere shortening initiates cellular senescence, which can lead to degeneration and atrophy of tissues, so the process is associated with a reduction in life expectancy and predisposition to a number of diseases. An accelerated rate of telomere attrition can serve as a predictor of life expectancy and health status of an individual. Telomere length is a complex phenotypic trait that is determined by many factors, including the genetic ones. Numerous studies (including genome-wide association studies, GWAS) indicate the polygenic nature of telomere length control. The objective of the present study was to characterize the genetic basis of the telomere length regulation using the GWAS data obtained during the studies of various human and other animal populations. To do so, a compilation of the genes associated with telomere length in GWAS experiments was collected, which included information on 270 human genes, as well as 23, 22, and 9 genes identified in the cattle, sparrow, and nematode, respectively. Among them were two orthologous genes encoding a shelterin protein (POT1 in humans and pot-2 in C. elegans). Functional analysis has shown that telomere length can be influenced by genetic variants in the genes encoding: (1) structural components of telomerase; (2) the protein components of telomeric regions (shelterin and CST complexes); (3) the proteins involved in telomerase biogenesis and regulating its activity; (4) the proteins that regulate the functional activity of the shelterin components; (5) the proteins involved in telomere replication and/or capping; (6) the proteins involved in the alternative telomere lengthening; (7) the proteins that respond to DNA damage and are responsible for DNA repair; (8) RNA-exosome components. The human genes identified by several research groups in populations of different ethnic origins are the genes encoding telomerase components such as TERC and TERT as well as STN1 encoding the CST complex component. Apparently, the polymorphic loci affecting the functions of these genes may be the most reliable susceptibility markers for telomere-related diseases. The systematized data about the genes and their functions can serve as a basis for the development of prognostic criteria for telomere length-associated diseases in humans. Information about the genes and processes that control telomere length can be used for marker-assisted and genomic selection in the farm animals, aimed at increasing the duration of their productive lifetime.
端粒是染色体的末端区域，可在细胞分裂时确保其稳定性。端粒缩短会引发细胞衰老，进而导致组织退化和萎缩，因此该过程与预期寿命缩短以及易患多种疾病有关。端粒损耗加速可作为个体预期寿命和健康状况的预测指标。端粒长度是一个复杂的表型性状，由许多因素决定，包括遗传因素。大量研究（包括全基因组关联研究，GWAS）表明端粒长度控制具有多基因性质。本研究的目的是利用在对各种人类和其他动物群体的研究中获得的GWAS数据，来描述端粒长度调控的遗传基础。为此，收集了GWAS实验中与端粒长度相关的基因汇编，其中包括270个人类基因的信息，以及分别在牛、麻雀和线虫中鉴定出的23个、22个和9个基因。其中有两个编码保护素蛋白的直系同源基因（人类中的POT1和秀丽隐杆线虫中的pot-2）。功能分析表明，端粒长度可能受到以下编码基因中的遗传变异影响：（1）端粒酶的结构成分；（2）端粒区域的蛋白质成分（保护素和CST复合物）；（3）参与端粒酶生物合成并调节其活性的蛋白质；（4）调节保护素成分功能活性的蛋白质；（5）参与端粒复制和/或加帽的蛋白质；（6）参与端粒延长替代途径的蛋白质；（7）对DNA损伤作出反应并负责DNA修复的蛋白质；（8）RNA外泌体成分。几个研究小组在不同种族群体中鉴定出的人类基因是编码端粒酶成分（如TERC和TERT）以及编码CST复合物成分的STN1的基因。显然，影响这些基因功能的多态性位点可能是端粒相关疾病最可靠的易感性标记。关于这些基因及其功能的系统化数据可作为制定人类端粒长度相关疾病预后标准的基础。关于控制端粒长度的基因和过程的信息可用于家畜的标记辅助选择和基因组选择，旨在延长其生产寿命。
