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Mol. Life Sci."],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2019s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4\u2009+\u2009T 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\u2009~\u2009500 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 \u201cgenetic wasteland\u201d, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.<\/jats:p>","DOI":"10.1007\/s00018-021-03822-w","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T23:28:20Z","timestamp":1618010900000},"page":"4019-4033","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Immune cells lacking Y chromosome show dysregulation of autosomal gene expression"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1489-1452","authenticated-orcid":false,"given":"Jan 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