Telomeres and disease PM Lansdorp Lundblad V (2002) Telomere maintenance without telomerase. Oncogene 21: 522–531 Ly H, Calado RT, Allard P, Baerlocher GM, Lansdorp PM, Young NS, Parslow TG (2005) Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 105: 2332–2339 Marrone A, Stevens D, Vulliamy T, Dokal I, Mason PJ (2004) Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via haploinsufﬁciency. Blood 104: 3936–3942 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 McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S et al (2008) Lung cancer susceptibility locus at 5p15.33. Nat Genet 40: 1404–1406 Michor F, Iwasa Y, Vogelstein B, Lengauer C, Nowak MA (2005) Can chromosomal instability initiate tumorigenesis? Semin Cancer Biol 15: 43–49 Mitchell JR, Wood E, Collins K (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402: 551–555 Nouspikel T, Hanawalt PC (2000) Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression. Mol Cell Biol 20: 1562–1570 Novelli EM, Ramirez M, Civin CI (1998) Biology of CD34+CD38 cells in lymphohematopoiesis. Leuk Lymphoma 31: 285–293 Potten CS, Owen G, Booth D (2002) Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 115 (Part 11): 2381–2388 Radak Z, Chung HY, Goto S (2008) Systemic adaptation to oxidative challenge induced by regular exercise. Free Radic Biol Med 44: 153–159 Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blondal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ et al (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41: 221–227 Riha K, McKnight TD, Grifﬁng LR, Shippen DE (2001) Living with genome instability: plant responses to telomere dysfunction. Science 291: 1797–1800 Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M, Lansdorp PM (1999) Telomere ﬂuor- escence 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 Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459: 262–265 Savage SA, Alter BP (2009) Dyskeratosis congenita. Hematol Oncol Clin North Am 23: 215–231 Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP (2008) TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet 82: 501–509 Schumacher B, Garinis GA, Hoeijmakers JH (2008) Age to survive: DNA damage and aging. Trends Genet 24: 77–85 Sedivy JM (2007) Telomeres limit cancer growth by inducing senescence: long-sought in vivo evidence obtained. Cancer Cell 11: 389–391 Shepherd BE, Kiem HP, Lansdorp PM, Dunbar CE, Aubert G, LaRochelle A, Seggewiss R, Guttorp P, Abkowitz JL (2007) Hematopoietic stem-cell behavior in nonhuman primates. Blood 110: 1806–1813 Smogorzewska A, de Lange T (2002) Different telomere damage signaling pathways in human and mouse cells. EMBO J 21: 4338–4348 Spalding KL, Bhardwaj RD, Buchholz BA, Druid H, Frisen J (2005) Retrospective birth dating of cells in humans. Cell 122: 133–143 Terstappen LW, Huang S, Safford M, Lansdorp PM, Loken MR (1991) Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38 progenitor cells. Blood 77: 1218–1227 Tippin B, Pham P, Goodman MF (2004) Error-prone replication for better or worse. Trends Microbiol 12: 288–295 von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27: 339–344 Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8: 275–283 Vulliamy T, Beswick R, Kirwan M, Marrone A, Digweed M, Walne A, Dokal I (2008) Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc Natl Acad Sci USA 105: 8073–8078 Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413: 432–435 Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I (2004) Disease anticipation is associated with progressive telo- mere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet 36: 447–449 Vulliamy TJ, Walne A, Baskaradas A, Mason PJ, Marrone A, Dokal I (2005) Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure. Blood Cells Mol Dis 34: 257–263 Walne AJ, Dokal I (2008) Dyskeratosis Congenita: a historical perspective. Mech Ageing Dev 129: 48–59 Walne AJ, Vulliamy T, Marrone A, Beswick R, Kirwan M, Masunari Y, Al-Qurashi FH, Aljurf M, Dokal I (2007) Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. Hum Mol Genet 16: 1619–1629 Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, Qureshi M, Dong Q, Gu X, Chen WV, Spitz MR, Eisen T, Amos CI, Houlston RS (2008) Common 5p15.33 and 6p21.33 variants inﬂuence lung cancer risk. Nat Genet 40: 1407–1409 Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA, Shah K, Sato M, Thomas RK, Barletta JA, Borecki IB, Broderick S, Chang AC, Chiang DY, Chirieac LR, Cho J et al (2007) Characterizing the cancer genome in lung adenocarcinoma. Nature 450: 893–898 Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M, Offner S, Dunant CF, Eshkind L, Bockamp E, Lio P, Macdonald HR, Trumpp A (2008) Hematopoietic stem cells reversibly switch from dormancy to self-renewal during home- ostasis and repair. Cell 135: 1118–1129 Wong LS, Oeseburg H, de Boer RA, van Gilst WH, van Veldhuisen DJ, van der Harst P (2009) Telomere biology in cardiovascular disease: the TERC / mouse as a model for heart failure and ageing. Cardiovasc Res 81: 244–252 Yamaguchi H, Baerlocher GM, Lansdorp PM, Chanock SJ, Nunez O, Sloand E, Young NS (2003) Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syn- drome. Blood 102: 916–918 Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS (2005) Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 352: 1413–1424 This is an open-access article distributed EMBO under the terms of the Creative Commons open Attribution License, which permits distri- bution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without speciﬁc permission. The EMBO Journal is published by Nature Publishing Group on behalf of European Molecular Biology Organization. This article is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Licence. [http://creativecommons.org/licenses/by-nc-nd/3.0] 2540 The EMBO Journal VOL 28 | NO 17 | 2009 & 2009 European Molecular Biology Organization