Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Jan;76(1):147-51.
doi: 10.1086/426734. Epub 2004 Nov 1.

Mapping of a major locus that determines telomere length in humans

Mariuca Vasa-Nicotera  1 , Scott Brouilette, Massimo Mangino, John R Thompson, Peter Braund, Jenny-Rebecca Clemitson, Andrea Mason, Clare L Bodycote, Stuart M Raleigh, Edward Louis, Nilesh J Samani
Affiliations

Mapping of a major locus that determines telomere length in humans

Mariuca Vasa-Nicotera et al. Am J Hum Genet. 2005 Jan.

Erratum in

  • Am J Hum Genet. 2005 Feb;76(2):373

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Age relationship and intersibling correlations for mean TRF length. A, Each subject’s mean TRF length, plotted as a function of the subject's age. Note the high interindividual variability in mean TRF length at any age. The regression lines show the mean decrease in TRF length with age of females (solid lines) and of males (dotted lines). The coefficient of variation in males was 9.6% and in women was 8.8%. B, The correlation in mean TRF length (unadjusted) between sib pairs.
Figure 2
Figure 2
Results of genome-scan analysis for mean TRF length. A, The peaks and corresponding LOD scores obtained on each chromosome from multipoint linkage analysis performed using SOLAR (see the “Methods” section of appendix A [online only] for details). B, A more detailed representation of the linkage observed on chromosome 12, with results from the additional markers typed in the region of the observed peak.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Ensembl, http://www.ensembl.org/ (for genetic distance between markers and identification of genes in the interval of interest)
    1. HapMap Project, http://www.hapmap.org/ (for SNP information)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for DDX11) - PubMed
    1. SNP Consortium Database, http://snp.cshl.org (for SNP information)

References

    1. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW, Harley CB (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 89:10114–10118 - PMC - PubMed
    1. Amann J, Kidd VJ, Lahti JM (1997) Characterization of putative human homologues of the yeast chromosome transmission fidelity gene, CHL1. J Biol Chem 272:3823–383210.1074/jbc.272.6.3823 - DOI - PubMed
    1. Benetos A, Okuda K, Lajemi M, Kimura M, Thomas F, Skurnick J, Labat C, Bean K, Aviv A (2001) Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 37:381–385 - PubMed
    1. Blackburn EH (2000) Telomere states and cell fates. Nature 408:53–5610.1038/35040500 - DOI - PubMed
    1. ——— (2001) Switching and signaling at the telomere. Cell 106:661–67310.1016/S0092-8674(01)00492-5 - DOI - PubMed

Supplemental References

    1. Abecasis GR, Cherny SS, Cookson WO, Cardon LR (2001) GRR: graphical representation of relationship errors. Bioinformatics 17:742–74310.1093/bioinformatics/17.8.742 - DOI - PubMed
    1. ——— (2002) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–10110.1038/ng786 - DOI - PubMed
    1. Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211 - PMC - PubMed
    1. Goring HH, Ott J (1997) Relationship estimation in affected sib pair analysis of late-onset diseases. Eur J Hum Genet 5:69–77 - PubMed
    1. Ke X, Hunt S, Tapper W, Lawrence R, Stavrides G, Ghori J, Whittaker P, Collins A, Morris AP, Bentley D, Cardon LR, Deloukas P (2004) The impact of SNP density on fine-scale patterns of linkage disequilibrium. Hum Mol Genet 13:577–58810.1093/hmg/ddh060 - DOI - PubMed

Publication types