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Am J Hum Genet. Nov 1994; 55(5): 876–882.
PMCID: PMC1918314

Genetic determination of telomere size in humans: a twin study of three age groups.

Abstract

Reduction of telomere length has been postulated to be a causal factor in cellular aging. Human telomeres terminate in tandemly arranged repeat arrays consisting of the (TTAGGG) motif. The length of these arrays in cells from human mitotic tissues is inversely related to the age of the donor, indicating telomere reduction with age. In addition to telomere length differences between different age cohorts, considerable variation is present among individuals of the same age. To investigate whether this variation can be ascribed to genetic influences, we have measured the size of terminal restriction fragments (TRFs) in HaeIII-digested genomic DNA from 123 human MZ and DZ twin pairs 2-95 years of age. The average rate of telomere shortening was 31 bp/year, which is similar to that observed by others. Statistical analysis in 115 pairs 2-63 years of age indicates a 78% heritability for mean TRF length in this age cohort. The individual differences in mean TRF length in blood, therefore, seem to a large extent to be genetically determined.

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Selected References

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  • Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW, Harley CB. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114–10118. [PMC free article] [PubMed]
  • Bender MA, Preston RJ, Leonard RC, Pyatt BE, Gooch PC. Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. II. Extension of age range. Mutat Res. 1989 Jun;212(2):149–154. [PubMed]
  • Biessmann H, Mason JM. Genetics and molecular biology of telomeres. Adv Genet. 1992;30:185–249. [PubMed]
  • Blackburn EH. Structure and function of telomeres. Nature. 1991 Apr 18;350(6319):569–573. [PubMed]
  • Boomsma DI, Kaptein A, Kempen HJ, Gevers Leuven JA, Princen HM. Lipoprotein(a): relation to other risk factors and genetic heritability. Results from a Dutch parent-twin study. Atherosclerosis. 1993 Feb;99(1):23–33. [PubMed]
  • Boomsma DI, Orlebeke JF, van Baal GC. The Dutch Twin Register: growth data on weight and height. Behav Genet. 1992 Mar;22(2):247–251. [PubMed]
  • Carson MJ, Hartwell L. CDC17: an essential gene that prevents telomere elongation in yeast. Cell. 1985 Aug;42(1):249–257. [PubMed]
  • Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 1992 May;11(5):1921–1929. [PMC free article] [PubMed]
  • Harley CB. Telomere loss: mitotic clock or genetic time bomb? Mutat Res. 1991 Mar-Nov;256(2-6):271–282. [PubMed]
  • Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990 May 31;345(6274):458–460. [PubMed]
  • Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC. Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990 Aug 30;346(6287):866–868. [PubMed]
  • Jeffreys AJ, Wilson V, Thein SL. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. [PubMed]
  • Kipling D, Cooke HJ. Hypervariable ultra-long telomeres in mice. Nature. 1990 Sep 27;347(6291):400–402. [PubMed]
  • Lange K, Weeks D, Boehnke M. Programs for Pedigree Analysis: MENDEL, FISHER, and dGENE. Genet Epidemiol. 1988;5(6):471–472. [PubMed]
  • Lange K, Westlake J, Spence MA. Extensions to pedigree analysis. III. Variance components by the scoring method. Ann Hum Genet. 1976 May;39(4):485–491. [PubMed]
  • Lundblad V, Szostak JW. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell. 1989 May 19;57(4):633–643. [PubMed]
  • Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989 Nov 3;59(3):521–529. [PubMed]
  • Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, Wu JR. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6622–6626. [PMC free article] [PubMed]
  • Olovnikov AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol. 1973 Sep 14;41(1):181–190. [PubMed]
  • Saccone S, De Sario A, Della Valle G, Bernardi G. The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4913–4917. [PMC free article] [PubMed]
  • Starling JA, Maule J, Hastie ND, Allshire RC. Extensive telomere repeat arrays in mouse are hypervariable. Nucleic Acids Res. 1990 Dec 11;18(23):6881–6888. [PMC free article] [PubMed]
  • Vaziri H, Schächter F, Uchida I, Wei L, Zhu X, Effros R, Cohen D, Harley CB. Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet. 1993 Apr;52(4):661–667. [PMC free article] [PubMed]

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