Understanding Significance Of Low Level Mosaicism In Rare Paediatric Disease Associated With Intellectual Disability And Autism

Research Opportunity
PhD
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Associate Professor David Godler david.godler@mcri.edu.au +61383416496 Personal web page
Co-supervisor Email Number Webpage
Professor David Amor david.amor@vcgs.org.au +61399366404 Personal web page
Dr Cas Simons cas.simons@mcri.edu.au +61399366488

Project Details

In the last five years the diagnosis of rare genetic diseases has been revolutionised by new DNA sequencing technologies. However, even after state-of-the-art genetic testing a specific cause remains elusive for more than half of affected children. In some individuals with a genetic disorder, the mutation that causes the disease is only present in a minority of cells of the body. This phenomenon, called mosaicism, can make standard genetic testing techniques ineffective resulting in missed diagnoses. Mosaicism may also be responsible for atypical and/or milder features of these disorders, which could mean that doctors may not recognise the features that should trigger appropriate genetic testing.

This could result in long delays in coming to the right diagnosis, with lost opportunities for early treatment and for accurate reproductive advice for the families. This project will focus on understanding of clinical and molecular significance of low level mosaicism across leading rare paediatric diseases associated with intellectual disability and autism including fragile X, Prader-Willi and Angelman syndromes. The work will be conducted as part of a large multidisciplinary team involving molecular genetics / genomics, clinical genetics, child psychology, neuroscience and bio-statistics expertise, with appropriate interdisciplinary training provided. The project will involve laboratory and clinical data collection and analyses on already recruited national and international cohorts.

The project with aim to understand:
1. How does mosaicism impact current rare disorder prevalence estimates, and our understanding of disorder natural history, and patient stratification?
2. How does prevalence of mosaicism for genetic mutations compare in asymptomatic children from the general population to cohorts of affected children referred for diagnostic testing?
3. How sensitive should molecular techniques be to be clinically meaningful?

While there is flexibility on whether the focus is primarily laboratory or clinical, preference will be given to candidates with interest and/or background in bioinformatics.



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine



Research Opportunities

PhD
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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