The Angelman (UBE3A/D15S10) probe is 108kb, labelled in red, covers most of the UBE3A gene and includes the D15S10 marker. The 15qter subtelomere specific probe (clone 154P1), labelled in green, allows identification of chromosome 15 and acts as a control probe.
In 70% of patients with Angelman syndrome (AS), a large de novo maternal deletion of 3-4Mb at 15q11.2-q13 is observed1,2,3. The remaining 30% of cases have underlying causes such as paternal uniparental disomy of the same region (~2%), imprinting defects (~2-3%) and mutations of the UBE3A gene1.
The UBE3A gene lies within the minimum AS critical region4 approximately 400kb telomeric to the SNRPN gene. It shows preferential expression of the maternal allele in the brain5 and is mutated in 20-30% of AS patients with normal methylation and biparental contribution of 15q11-13. It is considered to be one of the causative AS genes4,5.
The Angelman region probe covers approximately 108kb of genomic DNA, targets most of the UBE3A gene and includes the D15S10 locus. This probe may be used to identify deletions of the AS region, though it will not detect small intragenic deletions or mutations of UBE3A. The probe may also be used to help determine the nature of a Prader-Willi syndrome deletion detected with the SNRPN/Imprinting Centre probe (see LPU005). Large, 3-4Mb deletions of 15q11-13 will cause the deletion of both probe regions (SNRPN/IC and UBE3A/D15S10). Smaller deletions incorporating the IC and SNRPN, will not cause deletion of the UBE3A/D15S10 probe. These deletions may indicate a much higher risk of recurrence (possibly via grandmatrilineal inheritance) and carriers, and their families, may require further investigation6.
The quality of the products we have received from CytoCell have been excellent. The FISH probes they provide to us give intense, strong signals and are a pleasure to count. What has really stood out however has been the level of support and assistance provided by CytoCell’s application specialists. The team worked very closely alongside our own during the adoption of this product and spent many hours with us perfecting the technique, going above and beyond what I would expect during the transition period. Source BioScience absolutely demand high quality products and service to be able to deliver our results with confidence, and that is what we have received from CytoCell.
Laboratory Operations Manager, Source BioScience, UK