Mapping of a Major Locus that Determines Telomere Length in Humans

Abstract

Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus (or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/-SE) TRF was 81.9%+/-11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.

Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study

“…Several studies have investigated the heritability of LTL in twin and family studies. As in our study, the majority of these studies have indicated that LTL has a strong genetic component in (11,28,29). A recent meta-analysis reported a heritability estimate of 70% for LTL (11).…”

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

“…Another study comprising 258 sib-pairs returned a heritability estimate of 82%. 21 There is a need to reconcile these divergent estimates, which might in part be caused by differences in sample composition or TL assessments. 22 A remaining question that also needs to be addressed is the extent to which estimates of heritability based on twin data are comparable to those based on other relatives such as parents and offspring from multigenerational studies or non-twin sibling pairs.…”

Common variants near TERC are associated with leukocyte telomere length in the Chinese Han population

“…3 Telomere length varies between individuals of the same age, and is found to be inheritable in quantitative-trait linkage analyses of sib pairs. 4,5 Quantitative trait locus studies have mapped putative loci for telomere length to human chromosomes 3p26.1, 10q26.13, 12q12.22 and 14q23.2. [5][6][7] Telomerase is a large, mainly uncharacterized, RNA-protein complex that is responsible for the de novo synthesis and maintenance of telomere ends.…”

“…4,5 Quantitative trait locus studies have mapped putative loci for telomere length to human chromosomes 3p26.1, 10q26.13, 12q12.22 and 14q23.2. [5][6][7] Telomerase is a large, mainly uncharacterized, RNA-protein complex that is responsible for the de novo synthesis and maintenance of telomere ends. TERC is a main component of telomerase, which serves as a template for addition of multiple 6 bp (TTAGGG) telomere repeats.…”