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dc.contributor.authorMurray, Anna
dc.date.accessioned2020-04-29T10:42:06Z
dc.date.available2020-04-29T10:42:06Z
dc.date.issued2019-11
dc.identifier.citationThompson DJ [et al]. Genetic predisposition to mosaic Y chromosome loss in blood. Nature. 2019 Nov;575(7784):652-657en_US
dc.identifier.pmid31748747
dc.identifier.doi10.1038/s41586-019-1765-3
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621253
dc.description.abstractMosaic 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.en_US
dc.language.isoenen_US
dc.publisherNatureen_US
dc.relation.urlhttps://doi.org/10.1038/s41586-019-1765-3en_US
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen_US
dc.titleGenetic predisposition to mosaic Y chromosome loss in blooden_US
dc.typeJournal Articleen_US
dc.identifier.journalNatureen_US
dc.type.versionPublisheden_US


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