Contact information
Research groups
Websites
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MRC Weatherall Institute of Molecular Medicine
Research Institute
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MRC-Wellcome Trust Human Developmental Biology Resource
Chair
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PLoS Genetics
Associate Editor
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NIHR Oxford Biomedical Research Centre
Co-Theme Leader, Genomic Medicine
Andrew Wilkie
MA BM BCh DCH DM FRCP FMedSci FRS
Nuffield Professor of Pathology
- Honorary Consultant in Clinical Genetics
Skulls, limbs, and sperm: common themes in malformation
I've been employed as an Honorary Consultant in Clinical Genetics in Oxford since 1993, and my work has always been driven by the desire to give patients and families better answers to the questions they ask me in clinic. Working with plastic surgeons, my primary interest is in craniofacial malformations in children especially craniosynostosis, the premature fusion of the cranial sutures of the skull. By identifying the molecular genetic basis of these conditions, not only can we give families the answers they seek, we also gain fundamental knowledge about the details by which a human skull is built. A key early discovery (1995) was that Apert syndrome, in which the craniosynostosis occurs together with fusions of the fingers and toes, is caused by highly localised, recurrent mutations in the fibroblast growth factor receptor type 2 (FGFR2) gene. From this, two major research themes developed discovering other genetic causes of craniosynostosis, and finding out why certain genetic misprints such as the Apert FGFR2 mutations occur up to a thousand times more frequently than they should. The work on craniosynostosis has led to many important disease gene discoveries, for which genetic testing has been translated into the NHS. Work on the origins of the mutations led to the recognition of a novel process occurring in the testes, which we termed 'selfish spermatogonial selection', that provides a link between the origins of germline and somatic mutation. Current efforts focus on harnessing the technological revolution provided by next generation sequencing to identify even more new genetic causes of craniosynostosis. Using this information, we can explore the complex mechanisms by which a population of stem cells is maintained within the sutures to keep the suture open, yet continuously turns over to promote continued growth of the skull.
Key publications
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A Genetic-Pathophysiological Framework for Craniosynostosis.
Journal article
Twigg SRF. and Wilkie AOM., (2015), Am J Hum Genet, 97, 359 - 377
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New insights into craniofacial malformations.
Journal article
Twigg SRF. and Wilkie AOM., (2015), Hum Mol Genet, 24, R50 - R59
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Craniosynostosis.
Journal article
Johnson D. and Wilkie AOM., (2011), Eur J Hum Genet, 19, 369 - 376
Recent publications
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SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.
Journal article
Wood KA. et al, (2024), Am J Hum Genet
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A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark.
Journal article
Pei Y. et al, (2024), Genes (Basel), 15
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The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients.
Journal article
Watts LM. et al, (2024), Eur J Hum Genet
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Reassessing the association: evaluation of a polyalanine deletion variant of RUNX2 in non-syndromic sagittal and metopic craniosynostosis
Journal article
Walton I. et al, (2024), Journal of Anatomy
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Homozygous SMAD6 variants in two unrelated patients with craniosynostosis and radioulnar synostosis.
Journal article
Luyckx I. et al, (2024), J Med Genet, 61, 363 - 368
ORCID
0000-0002-2972-5481