Uniparental Disomy Detection in a Clinical Trio Genome Sequencing Cohort

March 10, 2026

Background

  • Uniparental disomy (UPD) refers to the inheritance of both homologous chromosomes from a single parent.
  • UPD can lead to diverse clinical outcomes through several mechanisms, including disruption of genomic
    imprinting, homozygosity for deleterious recessive alleles, or association with mosaic aneuploidy.
  • These conditions are often missed by targeted testing approaches, such as multigene panels, chromosomal microarray (CMA) and genome sequencing (GS) without parental sample. In particular, heterodisomy (hUPD) is more easily missed because no absence of heterozygosity (AOH) regions is present to alert to underlying UPD.
  • Here, we describe our experience with UPD detection by clinical trio GS.