Uniparental disomy analysis in trios using genome-wide SNP array and whole-genome sequencing data imply segmental uniparental isodisomy in general populations.

Whole chromosomal and segmental uniparental disomy (UPD) is one of the causes of imprinting disorder and other recessive disorders. Most investigations of UPD were performed only using cases with relevant phenotypic features and included few markers. However, the diagnosis of cases with segmental UPD requires a large number of molecular investigations. Currently, the accurate frequency of whole chromosomal and segmental UPD in a normal developing embryo is not well understood. Here, we present whole chromosome and segmental UPD analysis using single nucleotide polymorphism (SNP) microarray data of 173 mother-father-child trios (519 individuals) from six populations (including 170 HapMap trios). For two of these trios, we also investigated the possibility of shorter segmental UPD as a consequence of homologous recombination repair (HR) for DNA double strand breaks (DSBs) during the early developing stage using high-coverage whole-genome sequencing (WGS) data from 1000 Genomes Project. This could be overlooked by SNP microarray. We identified one obvious segmental paternal uniparental isodisomy (iUPD) (8.2 mega bases) in one HapMap sample from 173 trios using Genome-Wide Human SNP Array 6.0 (SNP6.0 array) data. However, we could not identify shorter segmental iUPD in two trios using WGS data. Finally, we estimated the rate of segmental UPD to be one per 173 births (0.578%) based on the UPD screening for 173 trios in general populations. Based on the autosomal chromosome pairs investigated, we estimate the rate of segmental UPD to be one per 3806 chromosome pairs (0.026%). These data imply the possibility of hidden segmental UPD in normal individuals.