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Am J Hum Genet. 2019 Nov 7;105(5):921-932. doi: 10.1016/j.ajhg.2019.09.016. Epub 2019 Oct 10.

Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population.

Author information

1
Center for Computational Molecular Biology, Brown University, 164 Angell St, Providence, RI 02912, USA; Ecology and Evolutionary Biology, Brown University, 80 Waterman St, Providence, RI 02912, USA; 23andMe, Inc., 223 N Mathilda Ave, Sunnyvale, CA 94086, USA. Electronic address: pnakka@wellesley.edu.
2
Center for Computational Molecular Biology, Brown University, 164 Angell St, Providence, RI 02912, USA; Ecology and Evolutionary Biology, Brown University, 80 Waterman St, Providence, RI 02912, USA.
3
Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
4
23andMe, Inc., 223 N Mathilda Ave, Sunnyvale, CA 94086, USA.
5
23andMe, Inc., 223 N Mathilda Ave, Sunnyvale, CA 94086, USA. Electronic address: fsathirapongsasuti@23andme.com.

Abstract

Meiotic nondisjunction and resulting aneuploidy can lead to severe health consequences in humans. Aneuploidy rescue can restore euploidy but may result in uniparental disomy (UPD), the inheritance of both homologs of a chromosome from one parent with no representative copy from the other. Current understanding of UPD is limited to ∼3,300 case subjects for which UPD was associated with clinical presentation due to imprinting disorders or recessive diseases. Thus, the prevalence of UPD and its phenotypic consequences in the general population are unknown. We searched for instances of UPD across 4,400,363 consented research participants from the personal genetics company 23andMe, Inc., and 431,094 UK Biobank participants. Using computationally detected DNA segments identical-by-descent (IBD) and runs of homozygosity (ROH), we identified 675 instances of UPD across both databases. We estimate that UPD is twice as common as previously thought, and we present a machine-learning framework to detect UPD using ROH. While we find a nominally significant association between UPD of chromosome 22 and autism risk, we do not find significant associations between UPD and deleterious traits in the 23andMe database.

KEYWORDS:

aneuploidy; identity-by-descent; runs of homozygosity; uniparental disomy

PMID:
31607426
PMCID:
PMC6848996
[Available on 2020-05-07]
DOI:
10.1016/j.ajhg.2019.09.016
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