Whole-genome sequencing for the identification of uniparental disomy

Uniparental disomy is a type of chromosomal variation leading to in which both homologous chromosomes or chromosomal regions are inherited from one parent. Such variations have been detected for all chromosomes. The frequency of uniparental disomies is estimated at 1 case per 2000 births. The causes of uniparental disomies include errors during meiosis, postzygotic errors, Robertsonian and reciprocal translocations. Clinical manifestations are associated with loss of heterozygosity for pathogenic genetic variants and defects in genomic imprinting.Currently, the diagnosis of uniparental disomy is performed using methods such as microsatellite analysis, chromosomal microarray analysis, methyl-sensitive PCR, methyl-specific amplification of a probe dependent on multiplex ligation and next-generation sequencing (NGS). The methods used nowadays separately do not allow for a definitive diagnosis of uniparental disomy. A combination of NGS method that simultaneously assesses the DNA methylation status and regions of loss of heterozygosity, in particular those based on fragmentation of genomic DNA by methyl-dependent restriction enzymes, with classical approaches such as methyl-sensitive PCR and microsatellite testing will enable rapid and accurate diagnosis of uniparental disomies.