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- Wilkie Group: Clinical Genetics Research Group
PhD; BSc (Hons)
I have worked as a postdoctoral scientist in the field of human genetics for several years (both in Melbourne, Australia and in the UK), working with a variety of genetic conditions including recessively inherited hearing loss and syndromes that specifically affect the craniofacial region. More recently I have been involved in trying to understand the genetics underlying the paediatric condition known as craniosynostosis, a condition in which children are born with the bones of the skull fused before they should be. This can result in the brain being unable to grow and expand to its full capacity, which in turn can cause an abnormal head shape and increased internal pressure on the growing brain, and in some cases can lead to more severe problems such as intellectual disability.
I currently work with human patient samples to try and identify the underlying genetic cause in patients with craniosynostosis. As the conditions I work with can vary in their presentation, traditional methods of genetic testing (based on tests associated with the patient's phenotype) can miss the genetic mistake that is causing the condition. I have been involved with sequencing the genome in patients suspected of carrying a faulty gene that is likely causing their condition. In patients where I have been able to identify a genetic mutation, this has not only provided an explanation of the cause of the condition in these patients for the first time, but in some cases it unexpectedly identified the potential for additional medical problems to develop, thereby helping to anticipate these through appropriate preventive measures. These findings are often entirely unanticipated, but have a direct and immediate impact on the decisions made in the medical care of the child and their family.
My research reflects the impact of using deep sequencing methods to identify the underlying genetic cause in patients that would otherwise have eluded routine clinical testing. My work also uses this data in the identification of new craniosynostosis disease genes which will lead to discoveries that will help to improve diagnosis and impact patient management strategies even further in the future. I have expertise in the following laboratory techniques:
- Basic molecular techniques including PCR, DNA cloning, DNA Sequencing analysis, High Resolution Melt, RNA isolation, cDNA synthesis, qPCR, GST-fusion protein production, Western Blot, H&E staining.
- Brightfield, Fluorescence, Confocal and Scanning Electron Microscopy.
- Generation and maintenance of transgenic & non-transgenic mouse lines, including breeding strategies and genotyping.
- Purification/isolation and analysis of human DNA from blood/tissue/saliva samples suitable for Next Generation Sequencing applications (IonTorrent and MiSeq/HiSeq).
- Whole mount in situ hybridisation in mouse, chicken and Xenopus embryos.
- Skeletal preparations of mouse and chicken embryos.
- Microinjection of mouse, Xenopus, zebrafish and chicken embryos, including the generation of expression constructs and modified ES cells by CRISPR/Cas9 editing.
- Hearing tests on mice (Auditory Brainstem Response).
- Transgenic mouse explant culture.
- Mammalian cell culture, transfection assays and AMAXA nucleofection technology.
Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.
Twigg SR. et al, (2016), Clin Genet, 90, 270 - 275
Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.
Fenwick AL. et al, (2016), Am J Hum Genet, 99, 125 - 138
A Recurrent Mosaic Mutation in SMO, Encoding the Hedgehog Signal Transducer Smoothened, Is the Major Cause of Curry-Jones Syndrome.
Twigg SRF. et al, (2016), Am J Hum Genet, 98, 1256 - 1265
Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability.
Twigg SR. et al, (2015), Am J Hum Genet, 97, 378 - 388
Olfr603, an orphan olfactory receptor, is expressed in multiple specific embryonic tissues.
Baker NL. et al, (2015), Gene Expr Patterns, 19, 30 - 35