RT Journal Article
SR Electronic
T1 Characterization of prevalence and health consequences of uniparental disomy in four million individuals from the general population
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 540955
DO 10.1101/540955
A1 Priyanka Nakka
A1 Samuel Pattillo Smith
A1 Anne H. O’Donnell-Luria
A1 Kimberly F. McManus
A1 23andMe Research Team
A1 Joanna L. Mountain
A1 Sohini Ramachandran
A1 J. Fah Sathirapongsasuti
YR 2019
UL http://biorxiv.org/content/early/2019/02/05/540955.abstract
AB 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 cases 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 in over four million 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. Here we present the first characterization of UPD prevalence in the general population, a machine-learning framework to detect UPD using ROH, and a novel association between autism and UPD of chromosome 22.