Skip to main content
SpringerLink
Log in

Allele-specific relative telomere lengths are inherited

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

An Erratum to this article was published on 01 March 2006

Abstract

Previous studies have indicated that single relative telomere lengths are defined in the zygote. In order to explore the possibility that single telomere lengths segregate in families, we compared relative telomere lengths obtained from allelic chromosome extremities transmitted from parent to child, representing a total of 31 independent meiotic events. We find a significant positive correlation of 0.65 (P=0.0004) between these telomere lengths, whereas the correlation between the non-transmitted parental homologue and the transmitted homologue in the child is not statistically significant (r=0.16; P=0.195). This study indicates that, even though there is a telomerase-mediated maintenance/elongation of telomeres in germ cells, allele-specific relative telomere lengths are preserved in the next generation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aviv A (2004) Telomeres and human aging: facts and fibs. Sci Aging Knowledge Environ 2004(51):43

    Article  Google Scholar 

  • Baird DM, Royle NJ (1997) Sequences from higher primates orthologous to the human Xp/Yp telomere junction region reveal gross rearrangements and high levels of divergence. Hum Mol Genet 6:2291–2299

    Article  PubMed  CAS  Google Scholar 

  • Baird DM, Coleman J, Rosser ZH, Royle NJ (2000) High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: implications for telomere biology and human evolution. Am J Hum Genet 66:235–250

    Article  PubMed  CAS  Google Scholar 

  • Baird DM, Rowson J, Wynford-Thomas D, Kipling D (2003) Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat Genet 33:203–207

    Article  PubMed  CAS  Google Scholar 

  • Baird DM, Britt-Compton B, Rowson J, Amso NN, Gregory L, Kipling D (2005) Telomere instability in the male germline. Hum Mol Genet 15(1):45–51

    Article  PubMed  Google Scholar 

  • Bekaert S, Derradji H, Baatout S (2004) Telomere biology in mammalian germ cells and during development. Dev Biol 274:15–30

    Article  PubMed  CAS  Google Scholar 

  • Blackburn EH (2001) Switching and signaling at the telomere. Cell 106:661–673

    Article  PubMed  CAS  Google Scholar 

  • Cawthon RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361:393–395

    Article  PubMed  CAS  Google Scholar 

  • Cerone MA, Londoño-Vallejo JA, Bacchetti S (2001) Telomere maintenance by telomerase and by recombination can coexist in human cells. Hum Mol Genet 10:1945–1952

    Article  PubMed  CAS  Google Scholar 

  • Chan SR, Blackburn EH (2004) Telomeres and telomerase. Philos Trans R Soc Lond B Biol Sci 359:109–121

    Article  PubMed  CAS  Google Scholar 

  • Chang S (2005) Modeling aging and cancer in the telomerase knockout mouse. Mutat Res 576(1–2):39–53

    PubMed  CAS  Google Scholar 

  • Chin K, de Solorzano CO, Knowles D, Jones A, Chou W, Rodriguez EG, Kuo WL, Ljung BM, Chew K, Myambo K, Miranda M, Krig S, Garbe J, Stampfer M, Yaswen P, Gray JW, Lockett SJ (2004) In situ analyses of genome instability in breast cancer. Nat Genet 36:984–988

    Article  PubMed  CAS  Google Scholar 

  • Coleman J, Baird DM, Royle NJ (1999) The plasticity of human telomeres demonstrated by a hypervariable telomere repeat array that is located on some copies of 16p and 16q. Hum Mol Genet 8:1637–1646

    Article  PubMed  CAS  Google Scholar 

  • d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426:194–198

    Article  PubMed  CAS  Google Scholar 

  • Der-Sarkissian H, Vergnaud G, Borde YM, Thomas G, Londono-Vallejo JA (2002) Segmental polymorphisms in the proterminal regions of a subset of human chromosomes. Genome Res 12:1673–1678

    Article  PubMed  CAS  Google Scholar 

  • Der-Sarkissian H, Bacchetti S, Cazes L, Londono-Vallejo JA (2004) The shortest telomeres drive karyotype evolution in transformed cells. Oncogene 23:1221–1228

    Article  PubMed  CAS  Google Scholar 

  • Fan Y, Linardopoulou E, Friedman C, Williams E, Trask BJ (2002) Genomic structure and evolution of the ancestral chromosome fusion site in 2q13–2q14.1 and paralogous regions on other human chromosomes. Genome Res 12:1651–1662

    Article  PubMed  CAS  Google Scholar 

  • Feldser DM, Hackett JA, Greider CW (2003) Telomere dysfunction and the initiation of genome instability. Nat Rev Cancer 3:623–627

    Article  PubMed  CAS  Google Scholar 

  • Gisselsson D, Jonson T, Petersen A, Strombeck B, Dal Cin P, Hoglund M, Mitelman F, Mertens F, Mandahl N (2001) Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors. Proc Natl Acad Sci USA 98:12683–12688

    Article  PubMed  CAS  Google Scholar 

  • Goldman F, Bouarich R, Kulkarni S, Freeman S, Du HY, Harrington L, Mason PJ, Londono-Vallejo A, Bessler M (2005) The effect of TERC haploinsufficiency on the inheritance of telomere length. Proc Natl Acad Sci USA 102(47):17119–17124

    Article  PubMed  CAS  Google Scholar 

  • Graakjaer J, Bischoff C, Korsholm L, Holstebroe S, Vach W, Bohr VA, Christensen K, Kolvraa S (2003) The pattern of chromosome-specific variations in telomere length in humans is determined by inherited, telomere-near factors and is maintained throughout life. Mech Ageing Dev 124:629–640

    Article  PubMed  CAS  Google Scholar 

  • Graakjaer J, Pascoe L, Der-Sarkissian H, Thomas G, Kolvraa S, Christensen K, Londoño-Vallejo J (2004) The relative lengths of individual telomeres are defined in the zygote and strictly maintained during life. Aging Cell 3:97–102

    Article  PubMed  CAS  Google Scholar 

  • Hamilton SE, Pitts AE, Katipally RR, Jia X, Rutter JP, Davies BA, Shay JW, Wright WE, Corey DR (1997) Identification of determinants for inhibitor binding within the RNA active site of human telomerase using PNA scanning. Biochemistry 36:11873–11880

    Article  PubMed  CAS  Google Scholar 

  • Hao LY, Strong MA, Greider CW (2004) Phosphorylation of H2AX at short telomeres in T cells and fibroblasts. J Biol Chem 279:45148–45154

    Article  PubMed  CAS  Google Scholar 

  • Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    Article  PubMed  CAS  Google Scholar 

  • Hathcock KS, Jeffrey Chiang Y, Hodes RJ (2005) In vivo regulation of telomerase activity and telomere length. Immunol Rev 205:104–113

    Article  PubMed  CAS  Google Scholar 

  • Hemann MT, Strong MA, Hao LY, Greider CW (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107:67–77

    Article  PubMed  CAS  Google Scholar 

  • Lansdorp PM, Verwoerd NP, van de Rijke FM, Dragowska V, Little MT, Dirks RW, Raap AK, Tanke HJ (1996) Heterogeneity in telomere length of human chromosomes. Hum Mol Genet 5:685–691

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Blasco M, Trimarchi J, Keefe D (2002) An essential role for functional telomeres in mouse germ cells during fertilization and early development. Dev Biol 249:74–84

    Article  PubMed  CAS  Google Scholar 

  • Londono-Vallejo JA, DerSarkissian H, Cazes L, Thomas G (2001) Differences in telomere length between homologous chromosomes in humans. Nucleic Acids Res 29:3164–3171

    Article  PubMed  CAS  Google Scholar 

  • Martens UM, Zijlmans JM, Poon SS, Dragowska W, Yui J, Chavez EA, Ward RK, Lansdorp PM (1998) Short telomeres on human chromosome 17p. Nat Genet 18:76–80

    Article  PubMed  CAS  Google Scholar 

  • Martens UM, Chavez EA, Poon SS, Schmoor C, Lansdorp PM (2000) Accumulation of short telomeres in human fibroblasts prior to replicative senescence. Exp Cell Res 256:291–299

    Article  PubMed  CAS  Google Scholar 

  • Meeker AK, Hicks JL, Iacobuzio-Donahue CA, Montgomery EA, Westra WH, Chan TY, Ronnett BM, De Marzo AM (2004) Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis. Clin Cancer Res 10:3317–3326

    Article  PubMed  CAS  Google Scholar 

  • Monfouilloux S, Avet-Loiseau H, Amarger V, Balazs I, Pourcel C, Vergnaud G (1998) Recent human-specific spreading of a subtelomeric domain. Genomics 51:165–176

    Article  PubMed  CAS  Google Scholar 

  • Nawrot TS, Staessen JA, Gardner JP, Aviv A (2004) Telomere length and possible link to X chromosome. Lancet 363:507–510

    Article  PubMed  CAS  Google Scholar 

  • Nergadze SG, Rocchi M, Azzalin CM, Mondello C, Giulotto E (2004) Insertion of telomeric repeats at intrachromosomal break sites during primate evolution. Genome Res 14:1704–1710

    Article  PubMed  CAS  Google Scholar 

  • Nordfjall K, Larefalk A, Lindgren P, Holmberg D, Roos G (2005) Telomere length and heredity: Indications of paternal inheritance. Proc Natl Acad Sci USA 102:16374–16378

    Article  PubMed  Google Scholar 

  • Perrem K, Colgin LM, Neumann AA, Yeager TR, Reddel RR (2001) Coexistence of alternative lengthening of telomeres and telomerase in hTERT-transfected GM847 cells. Mol Cell Biol 21:3862–3875

    Article  PubMed  CAS  Google Scholar 

  • Pommier JP, Sabatier L (2002) Telomere length distribution. Digital image processing and statistical analysis. Methods Mol Biol 191:33–63

    PubMed  CAS  Google Scholar 

  • Poon SS, Martens UM, Ward RK, Lansdorp PM (1999) Telomere length measurements using digital fluorescence microscopy. Cytometry 36:267–278

    Article  PubMed  CAS  Google Scholar 

  • Riethman H, Ambrosini A, Castaneda C, Finklestein J, Hu XL, Mudunuri U, Paul S, Wei J (2004) Mapping and initial analysis of human subtelomeric sequence assemblies. Genome Res 14:18–28

    Article  PubMed  CAS  Google Scholar 

  • Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M, Lansdorp PM (1999) Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med 190:157–167

    Article  PubMed  CAS  Google Scholar 

  • Schaetzlein S, Lucas-Hahn A, Lemme E, Kues WA, Dorsch M, Manns MP, Niemann H, Rudolph KL (2004) Telomere length is reset during early mammalian embryogenesis. Proc Natl Acad Sci USA 17:17

    Google Scholar 

  • Shay JW, Wright WE (2005) Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 26:867–874

    Article  PubMed  CAS  Google Scholar 

  • Slagboom PE, Droog S, Boomsma DI (1994) Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 55:876–882

    Google Scholar 

  • Trask BJ, Friedman C, Martin-Gallardo A, Rowen L, Akinbami C, Blankenship J, Collins C, Giorgi D, Iadonato S, Johnson F, Kuo WL, Massa H, Morrish T, Naylor S, Nguyen OT, Rouquier S, Smith T, Wong DJ, Youngblom J, van den Engh G (1998) Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. Hum Mol Genet 7:13–26

    Article  PubMed  CAS  Google Scholar 

  • Vasa-Nicotera M, Brouilette S, Mangino M, Thompson JR, Braund P, Clemitson JR, Mason A, Bodycote CL, Raleigh SM, Louis E, Samani NJ (2005) Mapping of a major locus that determines telomere length in humans. Am J Hum Genet 76:147–151

    Article  PubMed  CAS  Google Scholar 

  • Viera A, Parra MT, Rufas JS, Suja JA (2002) Size heterogeneity of telomeric DNA in mouse meiotic chromosomes. Cytogenet Genome Res 98:221–224

    Article  PubMed  CAS  Google Scholar 

  • von Zglinicki T (2001) Telomeres and replicative senescence: is it only length that counts? Cancer Lett 168:111–116

    Article  Google Scholar 

  • Zakian VA (1995) Telomeres: beginning to understand the end. Science 270:1601–1607

    Article  PubMed  CAS  Google Scholar 

  • Zhu L, Hathcock KS, Hande P, Lansdorp PM, Seldin MF, Hodes RJ (1998) Telomere length regulation in mice is linked to a novel chromosome locus. Proc Natl Acad Sci USA 95:8648–8653

    Article  PubMed  CAS  Google Scholar 

  • Zijlmans JM, Martens UM, Poon SS, Raap AK, Tanke HJ, Ward RK, Lansdorp PM (1997) Telomeres in the mouse have large inter-chromosomal variations in the number of T2AG3 repeats. Proc Natl Acad Sci USA 94:7423–7428

    Article  PubMed  CAS  Google Scholar 

  • Zou Y, Sfeir A, Gryaznov SM, Shay JW, Wright WE (2004) Does a sentinel or a subset of short telomeres determine replicative senescence? Mol Biol Cell 15:3709–3718

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank all the individuals who participated to the study as well as the people at the Fondation Jean Dausset involved in the organization and logistics of family recruitment and processing of blood samples. Thanks also to Leigh Pascoe for valuable discussions on statistical analyses. This work was supported in part by a grant from the Association pour la Recherche contre le Cancer (ARC) to J-A. L-V. (N°3588). We also thank the Danish Center of Molecular Gerontology for its support during J.G.’s PhD.

Author information

Authors and Affiliations

  1. Telomeres and Cancer Lab, UMR7147, CNRS-I, Curie-UPMC, Paris, France

    Jesper Graakjaer & José-Arturo Londoño-Vallejo

  2. Institute for Human Genetics, University of Aarhus, Aarhus, Denmark

    Jesper Graakjaer

  3. Fondation Jean Dausset CEPH, Paris, France

    Héra Der-Sarkissian, Jan Bayer & Gilles Thomas

  4. Commissariat à l’Energie Atomique, Fontenay-aux-Roses, France

    Annette Schmitz

  5. Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark

    Steen Kolvraa

Authors
  1. Jesper Graakjaer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Héra Der-Sarkissian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annette Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan Bayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gilles Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steen Kolvraa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José-Arturo Londoño-Vallejo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José-Arturo Londoño-Vallejo.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00439-006-0158-5

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Graakjaer, J., Der-Sarkissian, H., Schmitz, A. et al. Allele-specific relative telomere lengths are inherited. Hum Genet 119, 344–350 (2006). https://doi.org/10.1007/s00439-006-0137-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-006-0137-x

Keywords

Search

Navigation