Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population.
Am J Hum Genet
; 105(5): 921-932, 2019 11 07.
Article
em En
| MEDLINE
| ID: mdl-31607426
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 â¼3,300 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dissomia Uniparental
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article