Ontology highlight
ABSTRACT: Background
Uniparental disomy (UPD) is the inheritance of two homologous chromosomes from the same parent. UPD may result in clinical phenotypes when occurring on chromosomes with specific imprinting pattern, when leading to homozygosity of a deleterious recessive allele inherited from one carrier parent, or when associated with a mosaic aneuploidy. Due to the importance of UPD in genetic disease etiology, UPD analysis has started to be implemented in the context of exome sequencing (ES) or genome sequencing.Methods
We developed an in-house algorithm TRIPS (Trio Parentage/UPD Studies) to identify UPD events in trio ES cases. This method identifies regions with uniparental inheritance by utilizing the trio genotyping data obtained from the concurrent SNP array to delineate the parental origin of the SNPs in the proband.Results
We identified 16 UPD events from 2675 ES trios. Among those, four events led to imprinting disorders, seven unmasked a pathogenic/likely pathogenic variant in a recessive disease gene, and two were consistent with a mosaic genome wide paternal UPD pattern. Twelve of these UPD events directly contributed to the molecular diagnosis of the patients.Conclusion
Our study demonstrated the contribution of UPD to the molecular diagnosis in one clinical ES cohort, thus UPD analysis should be incorporated into routine clinical ES interpretation.
SUBMITTER: Wang L
PROVIDER: S-EPMC8606208 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Wang Lei L Liu Pengfei P Bi Weimin W Sim Teresa T Wang Xia X Walkiewicz Magdalene M Leduc Magalie Sophie MS Meng Linyan L Xia Fan F Eng Christine M CM Yang Yaping Y Yuan Bo B Dai Hongzheng H
Molecular genetics & genomic medicine 20210929 11
<h4>Background</h4>Uniparental disomy (UPD) is the inheritance of two homologous chromosomes from the same parent. UPD may result in clinical phenotypes when occurring on chromosomes with specific imprinting pattern, when leading to homozygosity of a deleterious recessive allele inherited from one carrier parent, or when associated with a mosaic aneuploidy. Due to the importance of UPD in genetic disease etiology, UPD analysis has started to be implemented in the context of exome sequencing (ES) ...[more]