Exome and whole genome sequencing to identify new genetic causes of skull malformations

Massively parallel genome sequencing has revolutionised the identification of Mendelian disease genes. This project will apply this approach to craniosynostosis, the premature fusion of the sutures of the skull.1,2. Oxford is one of 4 national referral centres for this condition, which has a prevalence of 1 in 2,250; we have one of the best characterised sample collections internationally, and we have a proven track record of success having identified and published more novel disease genes (MEGF8, TCF12, ERF, ZIC1, SMO, CDC45 and several others still undergoing investigation) than any other group working on this group of diseases. The UK’s Genomics England 100,000 Genomes project (https://www.genomicsengland.co.uk/), with which we are closely involved, will provide further opportunities for discovery during the course of the studentship. The aim of this project will be to identify new human disease genes in craniosynostosis and other craniofacial malformations and understand their associated clinical features and pathophysiology.