Genetic developmental disorders (DDs) that result in neurodevelopmental problems or major congenital organ malformations affect at least 5% of population and result in higher mortality, morbidity and socio-economic disadvantage. This impact is expected to be even more severe in countries such as India that have under-resourced healthcare and social-care systems. Considering the population of India, rare genetic developmental disorders pose a monumental medical and socio-economic burden.
Accurate genetic diagnosis of DDs is challenging, but aids in better management, treatment and prevention. Large-scale studies using new technologies such as whole exome/genome sequencing (WES/WGS) are beginning to uncover the genetic causes of DDs. However, still more than 50% of patients who undergo WES/WGS do not get an accurate result. One of the reasons for limited diagnostic utility of WGS is that the incidence of genetic disorders is determined by local population structure, history and cultural practices. This means that different genetic disorders will have different prevalence in the UK and in India. Hence, it is important to study the landscape of genetic disorders in a variety of populations. However, most large-scale genetic studies of DDs have primarily focussed on Western populations. Hence, there is an urgent need to perform a genetic study of DDs in the Indian population.
As part of this PhD project, the student will spend 2 years each at Manchester and Manipal to perform a systematic analysis of WES/WGS data to uncover the landscape of genetic DDs in India.
1. Bioinformatic analysis of WGS/WES data of a cohort of 1000 cases from Manipal (data already present).
2. Bioinformatic analysis of WGS/WES data of a cohort of 1000 cases from Manchester (data already present).
3. Comparative analysis of Manchester and Manipal cohorts.
4. Identification of novel genetic disorders that are novel or unique to the Manipal cohort.
5. Performing laboratory based studies to understand the underlying disease mechanism to identify potential therapies.
Training plan will provide student with a wide range of technical and academic skills including -
1. Large-scale bioinformatics analysis
2. Individual patient level variant interpretation and clinical correlation
3. Novel disease gene identification
4. Functional characterization of genetic diseases.
The student will join teams at two centres that have a long history of collaboration. The students will get to experience working in two different healthcare and research environments.
Candidates are expected to hold (or be about to obtain) an Upper Second class Honours degree (or equivalent) in a related area / subject.
If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - choose PhD Genomics. Full details on how to apply can be found on the GCRF website https://www.manchester.ac.uk/study/postgraduate-research/golden/gcrf/
The GCRF PhD studentship programme is a 4 year programme with integrated teaching certificate. There are up to 12 studentships available. Applicants can apply to one project which will start in either April or September 2020.
Funding for the programme will include tuition fees, an annual stipend at the minimum Research Councils UK rate (around £15,000 for 2019/20), a research training grant, training allowance and travel allowance.
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.