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Genetic predisposition to mosaic Y chromosome loss in blood
- Thompson, Deborah J (author)
- Genovese, Giulio (author)
-
- Halvardson, Jonatan, 1982- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Lars Forsberg
- show more...
- Ulirsch, Jacob C (author)
- Wright, Daniel J (author)
- Terao, Chikashi (author)
- Davidsson, Olafur B (author)
- Day, Felix R (author)
- Sulem, Patrick (author)
- Jiang, Yunxuan (author)
- Dennis, Joe (author)
- Dunlop, Malcolm G (author)
- Easton, Douglas F (author)
- Fisher, Victoria A (author)
- Zink, Florian (author)
- Houlston, Richard S (author)
- Kar, Siddhartha (author)
- Kerrison, Nicola D (author)
- Kinnersley, Ben (author)
- Kristjansson, Ragnar P (author)
- Law, Philip J (author)
- Li, Rong (author)
- Loveday, Chey (author)
- McCarroll, Steven A (author)
- Murakami, Yoshinori (author)
- Murray, Anna (author)
- Olszewski, Pawel (author)
- Rychlicka-Buniowska, Edyta (author)
- Scott, Robert A (author)
- Thorsteinsdottir, Unnur (author)
- Tomlinson, Ian (author)
- Turnbull, Clare (author)
- Wareham, Nicholas J (author)
- Gudbjartsson, Daniel F (author)
- Kamatani, Yoichiro (author)
- Hoffmann, Eva R (author)
- Jackson, Steve P (author)
- Stefansson, Kari (author)
- Auton, Adam (author)
- Ong, Ken K (author)
- Machiela, Mitchell J (author)
- Loh, Po-Ru (author)
- Chanock, Stephen J (author)
- Perry, John R B, 1974- (author)
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- (creator_code:org_t)
- 2019-11-20
- 2019
- English.
- In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 575, s. 652-657
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Medicinsk genetik
- Medical Genetics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Davidsson, Olafu ...
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- Sulem, Patrick
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- Houlston, Richar ...
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- Li, Rong
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Medical Genetics
- Articles in the publication
- Nature
- By the university
- Uppsala University
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