A new promising tool to interrogate DNA methylation at human imprinted regions has been developed by researchers from the University of Cambridge’s Department of Medical Genetics. ImprintSeq is a hybridization capture-based bisulfite sequencing panel designed and produced in collaboration with CEGX, NuGen and Tecan.
Genomic imprinting is an epigenetic process that controls the expression of more than 100 genes with a critical role in growth, metabolism and development. The loss of a single (or multiple) imprinting mark(s), causing altered expression of imprinted genes and is associated with congenital imprinting disorders (CIDs). This group of conditions includes disorders such as Angelman syndrome, Beckwith-Wiedemann syndrome, Silver-Russell syndrome and Prader-Willi syndrome but although these are distinct disorders they share overlapping clinical and epigenetic features. As yet, the role of disordered imprinting in human disease states is incompletely understood.
In order to better understand the role of genomic imprinting in CIDs and other conditions a multidisciplinary research team from the Department of Medical Genetics developed a new methylation test to comprehensively analyse 63 regions of the genome that are important for imprinting in humans. The lead author, postdoctoral fellow Dr Eguzkine Ochoa explained that the aim was to develop a cost-effective method that would be suitable for both research investigations and clinical genetic testing of patients with suspected CIDs. The results of ImprintSeq testing for the diagnosis of CIDs were similar to those obtained by clinical genetic laboratories (98.4% of sensitivity, 99.9% specificity) but ImprintSeq was also able to detect a subgroup of patients with CIDs that have methylation alterations at multiple imprinted loci (MLID). ImprintSeq was able to identify families with a child with a CID and MLID that might be at risk of having further affected children.
Dr Leonardo Bottolo, Reader in Statistics in Biomedicine oversaw the statistical analysis to ensure that ImprintSeq provided accurate and robust diagnostic results. Professor Eamonn Maher, Head of the Department of Medical Genetics reported that “we are now working with international research groups to extend our studies and to understand more fully the consequences of MLID for children and adults diagnosed with CIDs.”
The study, funded by the National Institute for Health Research Cambridge Biomedical Research Centre and Rosetrees Trust and published in the journal Genetics in Medicine, presents a highly promising tool for clinical diagnostics and research into the role of imprinting in human disease.
Reference
Eguzkine Ochoa et al., ‘ImprintSeq, a novel tool to interrogate DNA methylation at human imprinted regions and diagnose multilocus imprinting disturbance – Genetics in Medicine (gimjournal.org)‘ Genetics in Medicine (3 December 2021). DOI: 10.1016/j.gim.2021.10.011.