The individual\u2019s signature of telomere length distribution

Simon Toupance,Daphné Germain,Denis Villemonais,Anne Gegout-Petit,Eliane Albuisson,Athanase Benetos

doi:10.1038/s41598-018-36756-8

Abstract

Mean telomere length in human leukocyte DNA samples reflects the different lengths of telomeres at the ends of the 23 chromosomes and in an admixture of cells. However, only rudimentary information is available regarding the distribution of telomere lengths in all chromosomes and the different cell types in leukocyte samples. Understanding the configuration of leukocyte telomere length distribution (LTLD) could be helpful in capturing intrinsic elements that are not provided by the mean leukocyte telomere length (mLTL). The objective of this study was to analyse LTLD and its temporal variation in adults. Leukocyte samples were donated on two occasions (8 years apart) by 72 participants in the ADELAHYDE study. Telomere length was measured by Southern blotting of the terminal restriction fragments. Individuals with comparable mLTLs displayed different shapes of LTLDs. Inter-individual variation in LTLD shape was much larger than intra-individual variation in LTLD shape between baseline and follow-up leukocyte samples. These results show an important individual stability of LTLD shape over time indicating that each individual has a characteristic LTLD signature.

Highlights

Telomeres are non-coding nucleoprotein structures located at the end of chromosomes
Several methods have been developed to measure TL, including 1) Southern blot (SB) analysis of the terminal restriction fragments (TRF)11; 2) quantitative PCR whose output is expressed as the ratio of telomere product relative to a single copy gene product12; 3) fluorescent in situ hybridization (FISH) techniques, including quantitative FISH based on microscopy and flow FISH using flow cytometry13; 4) single telomere length analysis (STELA)[14] and telomere shortest length assay (TeSLA)[15], measurements at the single telomere level based on a combination of PCR and Southern blot
The central finding of this study is that individuals, even those with similar mean leukocyte telomere length (mLTL), display different leukocyte telomere length distribution (LTLD) shapes

Summary

Introduction

Telomeres are non-coding nucleoprotein structures located at the end of chromosomes. They protect loss of vital DNA sequences, block end-to-end fusions and facilitate distinguishing chromosome ends from DNA damage[1]. Telomere length (TL) displays a progressive shortening in replicating somatic cells due to the “end replication problem”[2]. These cells acquire critically short and dysfunctional telomeres that lead to growth arrest known as replicative senescence[3]. We hypothesized that the leukocyte telomere length distribution (LTLD) evolved over the 8-year follow-up period and that changes in shape would be noticeable. This hypothesis was based on the following two statements. Number of participants Age at baseline (years) Age at follow-up (years) Follow-up duration (years) mLTL at baseline (kb) mLTL at follow-up (kb) mLTL attrition (bp/year)

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Conclusion