Fast track — ArticlesTelomere length and possible link to X chromosome
Introduction
Telomeres consist of TTAGGG tandem repeats and telomere binding proteins that cap chromosomes and shield them from DNA-damage repair pathways.1 Telomeres undergo progressive attrition in cultured somatic cells because of the so-called end-replication problem. In utero, telomere length is similar in most tissues,2, 3 but during extrauterine life, telomeres progressively shorten in proliferative somatic cells and their length diminishes with age.4, 5, 6, 7 Telomere length is established by many factors, including cellular replicative history and telomerase—a reverse transcriptase consisting of an RNA component (hTR) and a catalytic protein component (hTERT) that has the ability to add telomere repeats to the ends of chromosomes.8 Based on studies in twins, telomere length seems to be familial, but little is known about its mode of inheritance.6, 7 We aimed to investigate the inheritance of telomere length.
Section snippets
Methods
We enrolled into our study a random sample of families living in a geographically defined area of northern Belgium, who were part of the family-based cohort of the Flemish Study on Environment, Genes, and Health Outcomes.9 We undertook our study according to the principles outlined in the Helsinki declaration for investigation of human participants. The ethics committee of the University of Leuven approved the study, and participants gave written informed consent.
We took blood samples from all
Results
Our multigeneration pedigrees spanned one (n=13), two (10), or three (8) generations and included 128 parents and 199 offspring (83 sons and 116 daughters). Mean age of parents and offspring was 51·7 years (SD 12·2) and 30·2 years (10·9), respectively. From the pedigrees, we identified 34 father-son pairs, 47 father-daughter pairs, 51 mother-son pairs, and 71 mother-daughter pairs. On the basis of ABO blood group and rhesus phenotypes, we did not detect any cases of false paternity.
TRF length
Discussion
The most plausible mechanism accounting for the high concordance of TRF length we noted between mothers and offspring and between fathers and daughters—but not between fathers and sons and between spouses—is an X-linked mechanism of inheritance. Findings of sensitivity analyses, with outliers excluded or including fictive parent-offspring pairs, suggested that our results were not attributable to chance, but did not completely exclude this possibility.
The X chromosome harbours the DKC1 gene
References (19)
Switching and signaling at the telomere.
Cell
(2001)- et al.
Telomere maintenance and disease.
Lancet
(2003) - et al.
Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita.
Blood Cells Mol Dis
(2001) - et al.
Telomere shortening in atherosclerosis.
Lancet
(2001) - et al.
Association between telomere length in blood and mortality in people aged 60 years or older.
Lancet
(2003) - et al.
Telomere length in the newborn.
Pediatr Res
(2002) - et al.
Synchrony in telomere length of the human fetus.
Hum Genet
(1998) - et al.
Telomere length predicts replicative capacity of human fibroblasts.
Proc Natl Acad Sci USA
(1992) - et al.
Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity.
Hypertension
(2001)
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