A rapid microarray based whole genome analysis for detection of uniparental disomy

Abstract

To date, uniparental disomy (UPD) with phenotypic relevance is described for different chromosomes and it is likely that additional as yet unidentified UPD phenotypes exist. Due to technical difficulties and limitations of time and resources, molecular analyses for UPD using microsatellite markers are only performed in cases with specific phenotypic features. In this study, we carried out a whole genome UPD screening based on a microarray genotyping technique. Six patients with the diagnosis of both complete or segmental UPD including Prader-Willi syndrome (PWS; matUPD15), Angelman syndrome (AS; patUPD15), Silver-Russell syndrome (SRS; matUPD7), Beckwith-Wiedemann syndrome (BWS; patUPD11p), pseudohypoparathyroidism (PHP; patUPD20q) and a rare chromosomal rearrangement (patUPD2p, matUPD2q), were genotyped using the GeneChip Human Mapping 10K Array. Our results demonstrate the presence of UPD in the patients with high efficiency and reveal clues about the mechanisms of UPD formation. We thus conclude that array based SNP genotyping is a fast, cost-effective, and reliable approach for whole genome UPD screening.

A new diagnostic workflow for patients with mental retardation and/or multiple congenital abnormalities: test arrays first

“…45 Two such cases of low-level mosaicism were reported in this study. Our patients with mosaic trisomy 13 the reported phenotypes of mosaic trisomy 13 and 14 (Figures 2). 46 -51 A major advantage of SNP array analysis is the extra SNP genotyping information, which enables the detection of copy number neutral chromosomal aberrations such as UPD and LOH.…”

Uniparental disomy: can SNP array data be used for diagnosis?

“…8 In the study, analysis of the proband and both parents allowed comparison of SNP transmissions. They identified UPD in all six patients, including three segmental UPDs (postzygotic events).…”

“…The power of CMA for the detection of copynumber variants has been well documented; however, very few studies have established the clinical use of SNP-based CMA for the detection of UPD. 8,9 metHOds UPD was investigated by conventional polymorphic microsatellite analysis after an abnormal methylation test result and the absence of a common microdeletion on chromosome 15, or because of a phenotype suggestive of UPD7 or UPD14. Microsatellite analysis was performed by polymerase chain reaction amplification on samples from the patient and both parents; all cases required at least three microsatellite markers consistent with failure to inherit a parental allele to be considered positive for UPD.…”

Genome-wide UPD screening in patients with intellectual disability

“…Current techniques for UPD detection (eg, methylation-specific PCR, methylation-specific MLPA and microsatellite analysis) are limited by number of markers and are generally restricted to distinct genomic regions or well-known imprinting syndromes. The usability of SNP microarrays for UPD detection has been proven and requires child-parent trio and special software for correct subclassification of UPDs [10][11][12] or parental exclusions from microsatellite analysis. UPD detection from trio experiments exceeds standard analysis that infers isodisomy from loss of heterozygosity 13 and requires specialized bioinformatic tools that automatically analyze occurrences of inheritance errors (Mendelian errors (MEs)) in large cohorts.…”