Molecular Detection of Uniparental Disomy

Cells with uniparental disomy (UPD) may have a normal cytogenetic karyotype but are unbalanced in terms of parental contribution. Diagnosis of UPD thus requires genotyping the ‘patient’ and parental DNA samples, i.e., evaluating the inheritance of molecular polymorphisms. This is most commonly preformed by microsatellite analysis which involves PCR amplification of polymorphic short tandem repeat loci with resolution of band sizes on a polyacrylamide gel. In some situations the UPD may be ‘segmental,’ i.e., involving only one region of the chromosome. Thus markers tested must be carefully chosen to ensure the region of UPD is not missed. For some chromosomes the presence of methylation differences between the two parental homologs can also be utilized to screen for UPD. The advantage to methylation based methods is that parental DNA is not necessary, and other imprinting defects may be picked up. The disadvantage is that UPD cannot be distinguished from abnormal methylation due to other causes by such methods alone.