Advancing episignature analysis for chromatin disorders

Epigenetic disorders of development (EDD) are associated with a range of clinical complications including developmental delay, growth and congenital anomalies, endocrine and others.  EDDs include both congenital imprinting disorders (CIDs) and conditions caused by germline pathogenic variants (GPVs; mutations) in genes that regulate chromatin structure /function (chromatin disorders=CD). The genetics of CDs are complex and genetic heterogeneity and variable genotype-phenotype relationships make the interpretation of variants of uncertain significance (VUS) in CD genes challenging. However, GPVs causing CDs are frequently associated with altered patterns of DNA methylation (episigntures) that can be detected in blood. Episignature analysis can resolve the pathogenicity of variants of uncertain significance (VUSs) but further algorithm development is required for full-scale clinical application. We have demonstrated that episignature analysis can inform VUS interpretation, have identified novel episignatures and demonstrated that episignatures might inform prognosis and insights into the mechanisms of disease. This project will extend these pilot findings by applying a novel state-of-the-art sequencing technique that provides both DNA sequence and CpG methylation status (Illumina 5-base sequencing) to CDs. This provides much more detailed analysis of methylation status than the methods currently used for episignature analysis and promises to improve the sensitivity and accuracy of episignature detection with the potential for direct translation into clinical diagnostics.

Relevant literature:
Lee S, Menzies L, Hay E et al. Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders. Hum Mol Genet. 2023;32:3123-3134

Lee S, Ochoa E, Badura-Stronka M, Donnelly D et al. Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome. Eur J Hum Genet. 2023;31:1040-1047

Ochoa E, Zvetkova I,  Lee S et al. Germline variants in UHRF1 are associated with multilocus imprinting disturbance in humans and mice. Proc Natl Acad Sci U S A. 2025;122):e2505884122
 

Candidates should have been awarded, or expect to achieve, EITHER:

a] a First or Upper Second Class award in their Undergraduate Degree (Bachelors or UG Masters) from a UK institution, in a subject judged by Aston to be relevant to the proposed research.

Alternativley

b] a Merit (or above)* in a Postgraduate Masters degree in a relevant subject AND an Undergraduate Degree (Bachelors or UG Masters), both from UK institutions.

*where appropriate.

Qualifications from overseas institutions will be also considered but performance must be equivalent to that described above, and the University reserves the right to ascertain this equivalence according to its own criteria.

Financial Support

This project covers the Home tuition fees. Candidates who do not have Home status will be responsible for the difference in tuition fees. Currently, the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7.  

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. Currently, the difference between ‘Home’ and the ‘Overseas’ tuition fees is £17,712 for 2026/7. As part of the application, you will be required to confirm that you will provide this additional funding. Please indicate this on the application form in the funding section.
 

Apply through our PhD application form.

When applying:

• For University College, please select Health and Life Sciences
• For Degree Programme, please select Research Health Sciences (including Optometry, Pharmacy, and Psychology Research Areas) and your preferred entry date.

Apply now

If you require further information about the application process please contact the Postgraduate Admissions team at pgr_admissions@aston.ac.uk

Supervisor: Professor Eamonn Maher

Associate Supervisor: Dr Sunwoo ‘Liv’ Lee and Dr Mohammed ‘Mo’ Elasrag

Contact information

For formal enquiries about this project contact Professor Eamonn Maher at e.maher@aston.ac.uk

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.