Stargardt disease due to mutations in the ABCA4 gene is the most frequent familial retinal dystrophy and is characterized by central vision loss due to the progressive degeneration of photoreceptor and retinal pigment epithelium cells. The age at onset and severity of Stargardt disease to a large degree depends on the types of mutations present in both copies of the ABCA4 gene.
A late age at onset (>40 yrs) can be observed when persons carry one severe and one mild mutation. For some mild mutations, when present together with a severe variant, it was shown that Stargardt disease may develop very late in life or may not develop at all. We also found that some combinations of ABCA4 mutations are found more often in females then in males. Together, these results led to the hypotheses that non-ABCA4 modifiers play an important role in the expression of Stargardt disease.
In this project the postdoc will search for genetic and non-genetic modifiers. Genetic modifiers will be searched through the comparison of genetic variants identified through whole genome sequencing in relevant patients and unaffected persons both from the Netherlands and through international collaborations. Non-genetic modifiers will be searched through the analysis of questionnaires filled in by these persons.
Tasks and responsibilities
- Systematically analyze whole genome sequencing data for variants that are enriched in Stargardt disease cases vs ethnically matched healthy controls and in severely affected Stargardt disease siblings compared to mildly affected siblings.
- Communicate with national and international ophthalmologists and geneticists to expand the patient cohort.
- Coordinate gene-specific and whole genome sequencing studies.
- Communicate results through scientific and laymen presentations.
- Take a leading role in writing manuscripts.
- Supervise junior scientists (BSc, MSc students, technicians) working in this project.
- Participate in educational tasks.