Abstract：Telomere is one of the basic functional elements for maintaining genome stability. Telomeres can become shorter due to cell divisions and environmental factors. Critically shortened telomeres eventually lead to cellular replicative senescence. Telomere length is an important parameter of telomere function, which determines the stability of chromosomes and the ability of cell proliferation. Currently multiple methods have been developed for the analysis of telomere length, including terminal restriction fragment (TRF) analysis, quantitative polymerase chain reaction (qPCR), single telomere length analysis (STELA), telomere shortest length assay (TeSLA) and telomere length combing assay (TCA) based on DNA, as well as quantitative fluorescence in situ hybridization (Q-FISH) based on cellular levels. Different analysis methods are applied to obtain different telomere relevant variables. In the review, we discuss the principle and application advantages of each telomere length analysis, which may help researchers select an optimal assessment approach to better address specific research questions about telomere in either model organisms or humans.
白玉杰, 张晓娟, 吴东颖. 端粒长度分析的研究现状及其应用前景[J]. 中国生物化学与分子生物学报, 2021, 37(10): 1290-1296.
BAI Yu-Jie, ZHANG Xiao-Juan, WU Dong-Ying. Research Status and Application Prospects of Telomere Length Analysis. Chinese Journal of Biochemistry and Molecular Biol, 2021, 37(10): 1290-1296.
[1] 张彬, 王长利. 端粒长度检测方法及其应用[J]. 生物技术通报(Zhang B, Wang CL. Methods of Measuring Telomere Length and Its Application[J]. Biotechnol Bull), 2016, 32(11): 93-98 [2] Yuan X, Dai M, Xu D. Telomere-related Markers for Cancer[J]. Curr Top Med Chem, 2020, 20(6): 410-432 [3] Wang Y, Suac L, Feigon J. Structural Biology of Telomerase[J]. Cold Spring Harb Perspect Biol, 2019, 11 (12): a032383 [4] Smith EM, Pendlebury DF, Nandakumar J. Structural biology of telomeres and telomerase[J]. Cell Mol Life Sci, 2020, 77(1): 61-79 [5] Pedro N, Diez M, Irene Garcia, et al. Analytical Validation of Telomere Analysis Technology for the High- Throughput Analysis of Multiple Telomere-Associated Variables[J]. Biol Proced Online, 2020, 22: 2 [6] Rizvi S, Raza ST, Mahdi F. Telomere Length Variations in Aging and Age-Related Diseases[J]. Curr Aging Sci, 2014, 7(3): 161-167 [7] Opresko PL, Shay JW. Telomere-associated aging disorders[J]. Ageing Res Rev, 2017, 33: 52-66 [8] Martínez P, Blasco MA. Heart-Breaking Telomeres[J]. Circ Res, 2018, 123(7): 787-802 [9] Niewisch MR, Savage SA. An update on the biology and management of dyskeratosis congenita and related telomere biology disorders[J]. Expert Rev Hematol, 2019, 12(12): 1037-1052 [10] Shay JW, Wright WE. Telomeres and telomerase: three decades of progress[J]. Nat Rev Genet, 2019, 20(5): 299-309 [11] Turner KJ, Vasu V, Griffin DK. Telomere Biology and Human Phenotype[J]. Cells, 2019, 8(1): 73 [12] Møller P, Wils RS, Jensen DM, et al. Telomere dynamics and cellular senescence: an emerging field in environmental and occupational toxicology[J]. Crit Rev Toxicol, 2018, 48(9): 761-788 [13] Hemann MT, Strong MA, Hao LY, et al. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability[J]. Cell, 2001, 107(1): 67-77 [14] Xu Z, Duc KD, Holcman D, et al. The length of the shortest telomere as the major determinant of the onset of replicative senescence[J]. Genetics, 2013, 194(4): 847-857 [15] Lee KH, Kimmel M. Stationary Distribution of Telomere Lengths in Cells with Telomere Length Maintenance and its Parametric Inference[J]. Bull Math Biol, 2020, 82(12): 150 [16] Vera E, De Jesus BB, Foronda M, et al. The Rate of Increase of Short Telomeres Predicts Longevity in Mammals[J]. Cell Rep, 2012, 2(4): 732-737 [17] Toupance S, Labat C, Temmar M, et al. Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis[J]. Hypertension, 2017, 70(2): 420-425 [18] Jenkins FJ, Kerr CM, Fouquerel E, et al. Modified Terminal Restriction Fragment Analysis for Quantifying Telomere Length Using In-gel Hybridization[J]. J Vis Exp, 2017, 2017(125): 56001 [19] Montpetit AJ, Alhareeri AA, Montpetit M, et al. Telomere Length: A Review of Methods for Measurement[J]. Nurs Res, 2014, 63(4): 289-299 [20] Chahine MN, Toupance S, El-Hakim S, et al. Telomere length and age-dependent telomere attrition: the blood-and-muscle model[J]. Can J Physiol Pharmacol, 2019, 97(4): 328-334 [21] Stefa A, Lamprokostopoulou A, Briana DD, et al. The effect of intrauterine growth on leukocyte telomere length at birth[J]. J Matern Fetal Neonatal Med, 2019, 32(23): 3948-3953 [22] Zhang WG, Jia LP, Ma J, et al. Peripheral blood leukocyte telomere length is associated with age but not renal function: A cross-sectional follow-up study[J]. J Nutr Health Aging, 2018, 22(2): 276-281 [23] Xu J, Songyang Z, Liu D, et al. Analysis of Average Telomere Length in Human Telomeric Protein Knockout Cells Generated by CRISPR/Cas9[J].Meth ods Mol Biol, 2017, 1587: 15-28 [24] Cawthon RM. Telomere measurement by quantitative PCR[J]. Nucleic Acids Res, 2002, 30(10): e47 [25] Cawthon RM. Telomere length measurement by a novel monochrome multiplex quantitative PCR method[J]. Nucleic Acids Res, 2009, 37(3): e21 [26] O′Callaghan NJ, Fenech M. A quantitative PCR method for measuring absolute telomere length[J]. Biol Proced Online, 2011, 13: 3 [27] Luo Y, Viswanathan R, Hande MP, et al. Massively parallel single-molecule telomere length measurement with digital real-time PCR[J]. Sci Adv, 2020, 6(34): eabb7944 [28] Lai TP, Wright WE, Shay JW. Comparison of telomere length measurement methods[J]. Philos Trans R Soc Lond B Biol Sci, 2018, 373(1741): 20160451 [29] Baird DM, Rowson J, Wynford-Thomas D, et al. Extensive allelic variation and ultrashort telomeres in senescent human cells[J]. Nat Genet, 2003, 33(2): 203-207 [30] Britt-Compton B, Rowson J, Locke M, et al. Structural stability and chromosome-specific telomere length is governed by cis-acting determinants in humans[J]. Hum Mol Genet, 2006, 15(5): 725-733 [31] Garcia-Martin I, Janssen AB, Jones RE, et al. Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis[J]. Placenta, 2017, 59: 61-68 [32] Aubert G, Hills M, Lansdorp PM. Telomere Length Measurement-caveats and a critical assessment of the available technologies and tools[J]. Mutat Res, 2012, 730(1-2): 59-67 [33] Bendix L, Horn PB, Jensen UB, et al. The load of short telomeres, estimated by a new method, Universal STELA, correlates with number of senescent cells[J]. Aging Cell, 2010, 9(3): 383-397 [34] Lai TP, Zhang N, Noh J, et al. A method for measuring the distribution of the shortest telomeres in cells and tissues[J]. Nat Commun, 2017, 8(1): 1356 [35] Robinson LRG Jr, Pimentel R, Wang F, et al. Impaired reproductive function and fertility preservation in a woman with a dyskeratosis congenita[J]. J Assist Reprod Genet, 2020, 37(5): 1221-1225 [36] Sawhney V, Campbell NG, Brouilette SW, et al. Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients-Potential markers of ventricular arrhythmia[J]. Int J Cardiol, 2016, 207:157-163 [37] Harbo M, Delaisse JM, Kjaersgaard-Andersen P, et al. The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis[J]. Mech Ageing Dev, 2013, 134(9): 367-372 [38] Kahl VFS, Allen JAM, Nelson CB, et al. Telomere Length Measurement by Molecular Combing[J]. Front Cell Dev Biol, 2020, 8: 493 [39] Lansdorp PM, Verwoerd NP, van de Rijke FM, et al. Heterogeneity in Telomere Length of Human Chromosomes[J]. Hum Mol Genet, 1996, 5(5): 685-691 [40] Narath R, Lörch T, Greulich-Bode KM, et al. Automatic telomere length measurements in interphase nuclei by IQ-FISH[J]. Cytometry A, 2005, 68(2): 113-120 [41] Vera E, Blasco MA. Beyond average: potential for measurement of short telomeres[J]. Aging(Albany NY), 2012, 4(6): 379-392 [42] Rufer N, Dragowska W, Thornbury G, et al. Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry[J]. Nat Biotechnol, 1998, 16(8): 743-747 [43] Baerlocher GM, Lansdorp PM. Telomere length measurements in leukocyte subsets by automated multicolor flow-FISH[J]. Cytometry A, 2003, 55(1): 1-6 [44] Ferreira MSV, Kirschner M, Halfmeyer I, et al. Comparison of flow‐FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies[J]. Ann N Y Acad Sci, 2020, 1466(1): 93-103
