• Login
    View Item 
    •   RD&E Research Repository Home
    • All RD&E publications by year
    • 2020 RD&E publications
    • View Item
    •   RD&E Research Repository Home
    • All RD&E publications by year
    • 2020 RD&E publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Large Copy-Number Variants in UK Biobank Caused by Clonal Hematopoiesis May Confound Penetrance Estimates

    Thumbnail
    URI
    https://rde.dspace-express.com/handle/11287/621526
    Author
    Tuke, M.
    Tyrrell, Jessica
    Ruth, K. S.
    Frayling, Timothy M.
    Weedon, M. N.
    Beaumont, Robin N.
    Wood, A. R.
    Murray, Anna
    Wright, Caroline F
    Date
    2020-08-06
    Journal
    American Journal of Human Genetics
    Type
    Journal Article
    Publisher
    Elsevier Science
    DOI
    10.1016/j.ajhg.2020.06.001
    Rights
    © 2020 American Society of Human Genetics.
    Metadata
    Show full item record
    Abstract
    Large copy-number variants (CNVs) are strongly associated with both developmental delay and cancer, but the type of disease depends strongly on when and where the mutation occurred, i.e., germline versus somatic. We used microarray data from UK Biobank to investigate the prevalence and penetrance of large autosomal CNVs and chromosomal aneuploidies using a standard CNV detection algorithm not designed for detecting mosaic variants. We found 160 individuals that carry >10 Mb copy number changes, including 56 with whole chromosome aneuploidies. Nineteen (12%) individuals had a diagnosis of Down syndrome or other developmental disorder, while 84 (52.5%) individuals had a diagnosis of hematological malignancies or chronic myeloproliferative disorders. Notably, there was no evidence of mosaicism in the blood for many of these large CNVs, so they could easily be mistaken for germline alleles even when caused by somatic mutations. We therefore suggest that somatic mutations associated with blood cancers may result in false estimates of rare variant penetrance from population biobanks.
    Citation
    Tuke M et al. Large Copy-Number Variants in UK Biobank Caused by Clonal Hematopoiesis May Confound Penetrance Estimates. Am J Hum Genet. 2020 Aug 6;107(2):325-329. doi: 10.1016/j.ajhg.2020.06.001. Epub 2020 Jun 22.
    Publisher URL
    https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(20)30189-0
    Collections
    • 2020 RD&E publications
    • Honorary contracts publications

    Browse

    All of RD&E Research RepositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    DSpace software copyright © 2002-2023  DuraSpace
    Contact Us | Send Feedback
    DSpace Express is a service operated by 
    Atmire NV