Estimating telomere length from whole genome sequence data

Zhihao Ding,Tim Spector,Massimo Mangino,Abraham Aviv,Richard Durbin

doi:10.1093/nar/gku181

Abstract

Telomeres play a key role in replicative ageing and undergo age-dependent attrition in vivo. Here, we report a novel method, TelSeq, to measure average telomere length from whole genome or exome shotgun sequence data. In 260 leukocyte samples, we show that TelSeq results correlate with Southern blot measurements of the mean length of terminal restriction fragments (mTRFs) and display age-dependent attrition comparably well as mTRFs.

Highlights

Telomeres cap the ends of chromosomes and are critical for the maintenance of genome integrity
We demonstrate our method on 260 leukocyte samples from the TwinsUK cohort [9] that have both Illumina 100 bp paired-end whole genome sequence and telomere length measurements using Southern blot mean length of terminal restriction fragments (mTRFs)
When TelSeq was applied to the TwinsUK data, the estimates of leukocyte telomere length (LTL) correlated well with the mTRFs measurements across a range of choices of k, with correlation ρ = 0.60 at the default threshold k = 7 (P < 10E−16; Figure 2a)

Summary

Introduction

Telomeres cap the ends of chromosomes and are critical for the maintenance of genome integrity. Shotgun sequence data contains sequencing reads from the telomeres just as any other region of the genome. Previous studies [7] have shown that information on telomere length is contained in the number of telomere motif copies (TTAGGG or CCCTAA) found in reads.

Results

Conclusion