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Immune cells lackin...
Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
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- Dumanski, Jan P. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Medical University of Gdańsk
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- Halvardson, Jonatan, 1982- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Davies, Hanna (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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Rychlicka-Buniowska, Edyta (author)
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- Mattisson, Jonas (author)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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- Torabi Moghadam, Behrooz (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Nagy, Noemi (author)
- Karolinska Institutet
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Węglarczyk, Kazimierz (author)
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Bukowska-Strakova, Karolina (author)
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- Danielsson, Marcus (author)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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Olszewski, Paweł (author)
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Piotrowski, Arkadiusz (author)
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Oerton, Erin (author)
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- Forsberg, Lars A., 1974- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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Przewoźnik, Marcin (author)
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Bełch, Łukasz (author)
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Grodzicki, Tomasz (author)
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Chłosta, Piotr L. (author)
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Imreh, Stefan (author)
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- Giedraitis, Vilmantas (author)
- Uppsala universitet,Geriatrik
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- Kilander, Lena (author)
- Uppsala universitet,Geriatrik
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- Nordlund, Jessica (author)
- Uppsala universitet,Molekylär medicin
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- Ameur, Adam (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Gyllensten, Ulf (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Johansson, Åsa (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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Józkowicz, Alicja (author)
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Siedlar, Maciej (author)
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Klich-Rączka, Alicja (author)
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Jaszczyński, Janusz (author)
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- Enroth, Stefan, 1976- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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Baran, Jarosław (author)
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- Ingelsson, Martin (author)
- Uppsala universitet,Geriatrik
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Perry, John R. B. (author)
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Ryś, Janusz (author)
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- Forsberg, Lars A., 1974- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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Belch, L (author)
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(creator_code:org_t)
- 2021-04-10
- 2021
- English.
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 78:8, s. 4019-4033
- Related links:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
Close
- Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- LOY
- Mosaic loss of chromosome Y
- Differential gene expression
- LATE
- LOY-associated transcriptional effects
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Dumanski, Jan P.
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Halvardson, Jona ...
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Davies, Hanna
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Rychlicka-Buniow ...
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Mattisson, Jonas
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Torabi Moghadam, ...
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show more...
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Nagy, Noemi
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Węglarczyk, Kazi ...
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Bukowska-Strakov ...
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Danielsson, Marc ...
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Olszewski, Paweł
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Piotrowski, Arka ...
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Oerton, Erin
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Forsberg, Lars A ...
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Przewoźnik, Marc ...
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Bełch, Łukasz
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Grodzicki, Tomas ...
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Chłosta, Piotr L ...
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Imreh, Stefan
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Giedraitis, Vilm ...
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Kilander, Lena
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Nordlund, Jessic ...
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Ameur, Adam
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Gyllensten, Ulf
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Johansson, Åsa
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Józkowicz, Alicj ...
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Siedlar, Maciej
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Klich-Rączka, Al ...
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Jaszczyński, Jan ...
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Enroth, Stefan, ...
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Baran, Jarosław
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Ingelsson, Marti ...
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Perry, John R. B ...
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Ryś, Janusz
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Belch, L
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Cellular and Mol ...
- By the university
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Uppsala University
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Karolinska Institutet