Mapping of a Major Locus that Determines Telomere Length in Humans
Mariuca Vasa-Nicotera,S. W. Brouilette,Massimo Mangino,John R. Thompson,Peter S. Braund,Jenny-Rebecca Clemitson,Andrea Mason,Clare L. Bodycote,Stuart M Raleigh,Edward J. Louis,Nilesh J. Samani +10 more
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TLDR
Mapping of the first locus that determines mean telomere length in humans is reported, and preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11, is presented.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.read more
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Candidate mechanisms for chemotherapy-induced cognitive changes.
TL;DR: It is suggested that shared genetic risk factors for the development of cancer and cognitive problems, including low-efficiency efflux pumps, deficits in DNA-repair mechanisms and/or a deregulated immune response, coupled with the effect of chemotherapy on these systems, might contribute to cognitive decline in patients after chemotherapy.
Journal ArticleDOI
Identification of seven loci affecting mean telomere length and their association with disease
Veryan Codd,Christopher P. Nelson,Eva Albrecht,Massimo Mangino,Joris Deelen,Jessica L. Buxton,Jouke-Jan Hottenga,Krista Fischer,Tõnu Esko,Ida Surakka,Linda Broer,Dale R. Nyholt,Irene Mateo Leach,Perttu Salo,Sara Hägg,Mary K. Matthews,Jutta Palmen,Giuseppe Danilo Norata,Paul F. O'Reilly,Danish Saleheen,Najaf Amin,Anthony J. Balmforth,Marian Beekman,Rudolf A. de Boer,Stefan Böhringer,Peter S. Braund,Paul Burton,Anton J. M. de Craen,Matthew Denniff,Yanbin Dong,Konstantinos Douroudis,Elena Dubinina,Johan G. Eriksson,Katia Garlaschelli,Dehuang Guo,Anna-Liisa Hartikainen,Anjali K. Henders,Jeanine J. Houwing-Duistermaat,Laura Kananen,Lennart C. Karssen,Johannes Kettunen,Norman Klopp,Vasiliki Lagou,Elisabeth M. van Leeuwen,Pamela A. F. Madden,Reedik Mägi,Patrik K. E. Magnusson,Satu Männistö,Satu Männistö,Mark I. McCarthy,Mark I. McCarthy,Mark I. McCarthy,Sarah E. Medland,Evelin Mihailov,Grant W. Montgomery,Ben A. Oostra,Aarno Palotie,Annette Peters,Helen Pollard,Anneli Pouta,Anneli Pouta,Inga Prokopenko,Samuli Ripatti,Veikko Salomaa,Veikko Salomaa,H. Eka D. Suchiman,Ana M. Valdes,Niek Verweij,Ana Viñuela,Xiaoling Wang,Xiaoling Wang,H-Erich Wichmann,Elisabeth Widen,Gonneke Willemsen,Margaret J. Wright,Kai Xia,Xiangjun Xiao,Dirk J. van Veldhuisen,Alberico L. Catapano,Martin D. Tobin,Alistair S. Hall,Alexandra I. F. Blakemore,Wiek H. van Gilst,Haidong Zhu,Haidong Zhu,Jeanette Erdmann,Muredach P. Reilly,Sekar Kathiresan,Sekar Kathiresan,Heribert Schunkert,Philippa J. Talmud,Nancy L. Pedersen,Markus Perola,Markus Perola,Markus Perola,Willem H. Ouwehand,Jaakko Kaprio,Nicholas G. Martin,Cornelia M. van Duijn,Iiris Hovatta,Iiris Hovatta,Christian Gieger,Andres Metspalu,Dorret I. Boomsma,Marjo-Riitta Järvelin,P. Eline Slagboom,John R Thompson,Tim D. Spector,Pim van der Harst,Nilesh J. Samani,Nilesh J. Samani +110 more
TL;DR: In this paper, a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals was carried out to identify seven loci, including five new loci associated with mean leukocyte telomere length (LTL) (P < 5 × 10−8).
Journal ArticleDOI
Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study
S. W. Brouilette,Jasbir S. Moore,Alex D. McMahon,John R. Thompson,Ian Ford,James Shepherd,Chris J. Packard,Nilesh J. Samani +7 more
TL;DR: In this article, the authors investigated whether mean leucocyte telomere length is a predictor of the development of coronary heart disease and found that individuals in the middle and lowest tertiles of telomeres were more at risk of developing a heart disease event than those in the highest tertile.
Identification of seven loci affecting mean telomere length and their association with disease
Veryan Codd,Christopher P. Nelson,Eva Albrecht,Massimo Mangino,Joris Deelen,Jessica L. Buxton,Jouke-Jan Hottenga,Krista Fischer,Tõnu Esko,Ida Surakka,Linda Broer,Dale R. Nyholt,Irene Mateo Leach,Perttu Salo,Sara Hägg,Mary K. Matthews,Jutta Palmen,Giuseppe Danilo Norata,Paul F. O'Reilly,Danish Saleheen,Najaf Amin,Anthony J. Balmforth,Marian Beekman,Rudolf A. de Boer,Stefan Böhringer,Peter S. Braund,Paul Burton,Anton J. M. de Craen,Matthew Denniff,Yanbin Dong,Konstantinos Douroudis,Elena Dubinina,Johan G. Eriksson,Katia Garlaschelli,Dehuang Guo,Anna-Liisa Hartikainen,Anjali K. Henders,Jeanine J. Houwing-Duistermaat,Laura Kananen,Lennart C. Karssen,Johannes Kettunen,Norman Klopp,Vasiliki Lagou,Elisabeth M. van Leeuwen,Pamela A. F. Madden,Reedik Maegi,Patrik K. E. Magnusson,Satu Männistö,Mark I. McCarthy,Sarah E. Medland,Evelin Mihailov,Grant W. Montgomery,Ben A. Oostra,Aarno Palotie,Annette Peters,Helen Pollard,Anneli Pouta,Inga Prokopenko,Samuli Ripatti,Veikko Salomaa,H. Eka D. Suchiman,Ana M. Valdes,Niek Verweij,Ana Viñuela,Xiaoling Wang,H-Erich Wichmann,Elisabeth Widen,Gonneke Willemsen,Margaret J. Wright,Kai Xia,Xiangjun Xiao,Dirk J. van Veldhuisen,Alberico L. Catapano,Martin D. Tobin,Alistair S. Hall,Alexandra I. F. Blakemore,Wiek H. van Gilst,Haidong Zhu,Jeanette Erdmann,Muredach P. Reilly,Sekar Kathiresan,Heribert Schunkert,Philippa J. Talmud,Nancy L. Pedersen,Markus Perola,Willem H. Ouwehand,Jaakko Kaprio,Nicholas G. Martin,Cornelia M. van Duijn,Iris Hovatta,Christian Gieger,Andres Metspalu,Dorret I. Boomsma,Marjo-Riitta Järvelin,P. Eline Slagboom,John R Thompson,Tim D. Spector,Pim van der Harst,Nilesh J. Samani +98 more
TL;DR: In this article, a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals was carried out to identify seven loci, including five new loci associated with mean leukocyte telomere length (LTL).
Journal ArticleDOI
Telomere shortening in familial and sporadic pulmonary fibrosis
Jennifer T. Cronkhite,Chao Xing,Ganesh Raghu,Kelly Chin,Fernando Torres,Randall L. Rosenblatt,Christine Kim Garcia +6 more
TL;DR: A significant fraction of individuals with pulmonary fibrosis have short telomere lengths that cannot be explained by coding mutations in telomerase, which may be a marker for an increased predisposition toward the development of this age-associated disease.
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