Dr Mark Corbett

Mark Corbett
Adelaide Medical School
Faculty of Health and Medical Sciences

My primary research aim is to map the genetic landscape of neurological disorders, with a view to understanding the basic biology of cognition and to provide an in-road for therapies for these devastating disorders.

My PhD training was centred on the analysis of a transgenic mouse model for the most commonly observed congenital myopathy (nemaline myopathy). This project showed me the value and power of an accurate model to facilitate understanding of the aetiology of human genetic disease from physiology down to the molecular level.

I have built my career in human genetics by implicating a host of new genes in intellectual disability, epilepsy and other neurodevelopmental disorders. These individually rare but collectively common disorders affect about 3% of the population and have a huge social, financial and welfare burden on those affected.

My research group uses massively parallel sequencing data to identify novel disease causing mutations and measure gene expression with bioinformatics analysis pipelines developed in-house. We use the accumulated genetic, gene expression, protein interaction and animal disease model data extracted from public databases to prioritise which genes are most likely to be the culprits in disease causation. The genes we have found to date tie the aetiology of neurodevelopmental disorders to fundamental cell biology processes such as gene expression, RNA metabolism, protein degradation and regulation of the cytoskeleton. Our work has contributed to the translation of these new technologies into clinical genetic testing.

On discovery of a mutation, we further test its disease causing capacity by designing and carrying out experiments using molecular and cell biology based assays. These assays use cell lines derived directly from patients where possible but we also make use of animal models when necessary and appropriate.

Connect with me

Dr Mark Corbett

My primary research aim is to map the genetic landscape of neurological disorders, with a view to understanding the basic biology of cognition and to provide an in-road for therapies for these devastating disorders.

My PhD training was centred on the analysis of a transgenic mouse model for the most commonly observed congenital myopathy (nemaline myopathy). This project showed me the value and power of an accurate model to facilitate understanding of the aetiology of human genetic disease from physiology down to the molecular level.

I have built my career in human genetics by implicating a host of new genes in intellectual disability, epilepsy and other neurodevelopmental disorders. These individually rare but collectively common disorders affect about 3% of the population and have a huge social, financial and welfare burden on those affected.

My research group uses massively parallel sequencing data to identify novel disease causing mutations and measure gene expression with bioinformatics analysis pipelines developed in-house. We use the accumulated genetic, gene expression, protein interaction and animal disease model data extracted from public databases to prioritise which genes are most likely to be the culprits in disease causation. The genes we have found to date tie the aetiology of neurodevelopmental disorders to fundamental cell biology processes such as gene expression, RNA metabolism, protein degradation and regulation of the cytoskeleton. Our work has contributed to the translation of these new technologies into clinical genetic testing.

On discovery of a mutation, we further test its disease causing capacity by designing and carrying out experiments using molecular and cell biology based assays. These assays use cell lines derived directly from patients where possible but we also make use of animal models when necessary and appropriate.

Education

Date Institution name Country Title
The University of Adelaide Australia B.Sc(Hons)
The University of Sydney Australia PhD

Certifications

Date Title Institution name Country
2016 HLTAID003 Apply First Aid Divers Alert Network Asia Pacific

Research Interests

Bioinformatics, Genome Structure and Regulation, Genomics, Neurogenetics

Journals

Year Citation
2017 Pham, D., Tan, C., Homan, C., Kolc, K., Corbett, M., McAninch, D. ... Gecz, J. (2017). Protocadherin 19 (PCDH19) interacts with paraspeckle protein NONO to co-regulate gene expression with estrogen receptor alpha (ERα). Human Molecular Genetics, 26, 11, 2042-2052.
10.1093/hmg/ddx094
2017 Carroll, R., Kumar, R., Shaw, M., Slee, J., Kalscheuer, V., Corbett, M. & Gecz, J. (2017). Variant in the X-chromosome spliceosomal gene GPKOW causes male-lethal microcephaly with intrauterine growth restriction. European Journal of Human Genetics, 25, 9, 1078-1082.
10.1038/ejhg.2017.97
2017 Corbett, M., Turner, S., Gardner, A., Silver, J., Stankovich, J., Leventer, R. ... Gecz, J. (2017). Familial epilepsy with anterior polymicrogyria as a presentation of COL18A1 mutations. European Journal of Medical Genetics, 60, 8, 437-443.
10.1016/j.ejmg.2017.06.002
2016 Hu, H., Haas, S., Chelly, J., Van Esch, H., Raynaud, M., De Brouwer, A. ... Montjean, R. (2016). X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. Molecular Psychiatry, 21, 1, 133-148.
10.1038/mp.2014.193
2016 Kumar, R., Ha, T., Pham, D., Shaw, M., Mangelsdorf, M., Friend, K. ... Gecz, J. (2016). A non-coding variant in the 5' UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disability. European Journal of Human Genetics, 24, 11, 1612-1616.
10.1038/ejhg.2016.46
2016 Corbett, M., Bellows, S., Li, M., Carroll, R., Micallef, S., Carvill, G. ... Gecz, J. (2016). Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy. Neurology, 87, 19, 1975-1984.
10.1212/WNL.0000000000003309
2016 Balestrini, S., Milh, M., Castiglioni, C., Lüthy, K., Finelli, M., Verstreken, P. ... Kayserili, H. (2016). TBC1D24 genotype-phenotype correlation. Neurology, 87, 1, 77-85.
10.1212/WNL.0000000000002807
2016 Afawi, Z., Oliver, K., Kivity, S., Mazarib, A., Blatt, I., Neufeld, M. ... Jackson, G. (2016). Multiplex families with epilepsy: success of clinical and molecular genetic characterization. Neurology, 86, 8, 713-722.
10.1212/WNL.0000000000002404
2016 Ha, T., Sadleir, L., Mandelstam, S., Paterson, S., Scheffer, I., Gecz, J. & Corbett, M. (2016). A mutation in COL4A2 causes autosomal dominant porencephaly with cataracts. American Journal of Medical Genetics Part A, 170, 4, 1059-1063.
10.1002/ajmg.a.37527
2016 Henden, L., Freytag, S., Afawi, Z., Baldassari, S., Berkovic, S., Bisulli, F. ... Striano, P. (2016). Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2. Human Genetics, 135, 10, 1117-1125.
10.1007/s00439-016-1700-8
2016 Friez, M., Brooks, S., Stevenson, R., Field, M., Basehore, M., Adès, L. ... Schwartz, C. (2016). HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an X-chromosome exome sequencing study. BMJ Open, 6, 4, e009537-1-e009537-9.
10.1136/bmjopen-2015-009537
2016 Myers, C., McMahon, J., Schneider, A., Petrovski, S., Allen, A., Carvill, G. ... Eichler, E. (2016). De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies. American Journal of Human Genetics, 99, 2, 287-298.
10.1016/j.ajhg.2016.06.003
2016 McPherson, N., Fullston, T., Kang, W., Sandeman, L., Corbett, M., Owens, J. & Lane, M. (2016). Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant/vitamin food fortification in fathers. Scientific Reports, 6, 1, 1-14.
10.1038/srep27010
2015 Kumar, R., Corbett, M., Smith, N., Jolly, L., Tan, C., Keating, D. ... Gecz, J. (2015). Homozygous mutation of STXBP5L explains an autosomal recessive infantile-onset neurodegenerative disorder. Human Molecular Genetics, 24, 7, 2000-2010.
10.1093/hmg/ddu614
2015 Gecz, J. & Corbett, M. (2015). Developmental disorders: deciphering exomes on a grand scale. The Lancet, 385, 9975, 1266-1267.
10.1016/S0140-6736(14)62122-X
2015 McMichael, G., Bainbridge, M., Haan, E., Corbett, M., Gardner, A., Thompson, S. ... MacLennan, A. (2015). Whole-exome sequencing points to considerable genetic heterogeneity of cerebral palsy. Molecular Psychiatry, 20, 2, 176-182.
10.1038/mp.2014.189
2015 Kumar, R., Corbett, M., Van Bon, B., Woenig, J., Weir, L., Douglas, E. ... Zhao, H. (2015). THOC2 mutations implicate mRNA-export pathway in X-linked intellectual disability. American Journal of Human Genetics, 97, 2, 302-310.
10.1016/j.ajhg.2015.05.021
2015 Kumar, R., Corbett, M., Van Bon, B., Gardner, A., Woenig, J., Jolly, L. ... Ullmann, R. (2015). Increased STAG2 dosage defines a novel cohesinopathy with intellectual disability and behavioral problems. Human Molecular Genetics, 24, 25, 7171-7181.
10.1093/hmg/ddv414
2015 Haines, B., Hughes, J., Corbett, M., Shaw, M., Innes, J., Patel, L. ... Thomas, P. (2015). Interchromosomal insertional translocation at Xq26.3 alters SOX3 expression in an individual with XX male sex reversal. The Journal of Clinical Endocrinology & Metabolism, 100, 5, E815-E820.
10.1210/jc.2014-4383
2015 Tan, C., Shard, C., Ranieri, E., Hynes, K., Pham, D., Leach, D. ... Gecz, J. (2015). Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency. Human Molecular Genetics, 24, 18, 5250-5259.
10.1093/hmg/ddv245
2015 Grozeva, D., Carss, K., Spasic-Boskovic, O., Tejada, M., Gecz, J., Shaw, M. ... Hurles, M. (2015). Targeted next-generation sequencing analysis of 1,000 individuals with intellectual disability. Human Mutation, 36, 12, 1197-1204.
10.1002/humu.22901
2015 Song, H., Bettegowda, A., Oliver, D., Yan, W., Phan, M., De Rooij, D. ... Wilkinson, M. (2015). shRNA off-target effects in vivo: impaired endogenous siRNA expression and spermatogenic defects. H. White-Cooper (Ed.). PLoS One, 10, 3, e0118549-1-e0118549-23.
10.1371/journal.pone.0118549
2015 Corbett, M., Dudding-Byth, T., Crock, P., Botta, E., Christie, L., Nardo, T. ... Field, M. (2015). A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A. Journal of Medical Genetics, 52, 4, 269-274.
10.1136/jmedgenet-2014-102418
2013 Jolley, A., Corbett, M., McGregor, L., Waters, W., Brown, S., Nicholl, J. & Yu, S. (2013). De novo intragenic deletion of the autism susceptibility candidate 2 (AUTS2) gene in a patient with developmental delay: A case report and literature review. American Journal of Medical Genetics. Part A, 161, 6, 1508-1512.
10.1002/ajmg.a.35922
2013 Fullston, T., Ohlsson Teague, E., Mc Pherson, N., De Blasio, M., Mitchell, M., Corbett, M. ... Lane, M. (2013). Paternal obesity initiates metablic disturbances in two generations of mice with incomplete penetrance to the F₂ generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB Journal, 27, 10, 4226-4243.
10.1096/fj.12-224048
2013 Lomax, L., Bayly, M., Hjalgrim, H., Moller, R., Vlaar, A., Aaberg, K. ... Dibbens, L. (2013). 'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation. Brain, 136, 4, 1146-1154.
10.1093/brain/awt021
2013 Afawi, Z., Mandelstam, S., Korczyn, A., Kivity, S., Walid, S., Shalata, A. ... Jackson, G. (2013). TBC1D24 mutation associated with focal epilepsy, cognitive impairment and a distinctive cerebro-cerebellar malformation. Epilepsy Research, 105, 1-2, 240-244.
10.1016/j.eplepsyres.2013.02.005
2013 Dibbens, L., de Vries, B., Donatello, S., Heron, S., Hodgson, B., Chintawar, S. ... Cossette, P. (2013). Mutations in DEPDC5 cause familial focal epilepsy with variable foci. Nature Genetics, 45, 5, 546-U123.
10.1038/ng.2599
2012 Huang, L., Jolly, L., Willis-Owen, S., Gardner, A., Sharma, R., Douglas, E. ... Gecz, J. (2012). A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability. American Journal of Human Genetics, 91, 4, 694-702.
10.1016/j.ajhg.2012.08.011
2012 Heron, S., Grinton, B., Kivity, S., Afawi, Z., Zuberi, S., Hughes, J. ... Dibbens, L. (2012). PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome. American Journal of Human Genetics, 90, 1, 152-160.
10.1016/j.ajhg.2011.12.003
2012 Field, M., Scheffer, I., Gill, D., Wilson, M., Christie, L., Shaw, M. ... Gecz, J. (2012). Expanding the molecular basis and phenotypic spectrum of X-linked Joubert syndrome associated with OFD1 mutations. European Journal of Human Genetics, 20, 7, 806-809.
10.1038/ejhg.2012.9
2012 Froyen, G., Belet, S., Martinez, F., Santos-Reboucas, C., Declercq, M., Verbeeck, J. ... Marynen, P. (2012). Copy-number gains of HUWE1 due to replication-and recombination-based rearrangements. American Journal of Human Genetics, 91, 2, 252-264.
10.1016/j.ajhg.2012.06.010
2012 Nguyen, L., Jolly, L., Shoubridge, C., Chan, W., Huang, L., Laumonnier, F. ... Gecz, J. (2012). Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability. Molecular Psychiatry, 17, 11, 1103-1115.
10.1038/mp.2011.163
2011 Corbett, M., Schwake, M., Bahlo, M., Dibbens, L., Lin, M., Gandolfo, L. ... Berkovic, S. (2011). A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia. American Journal of Human Genetics, 88, 5, 657-663.
10.1016/j.ajhg.2011.04.011
2011 Bruno, I., Karam, R., Huang, L., Bhardwaj, A., Lou, C., Shum, E. ... Wilkinson, M. (2011). Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay. Molecular Cell, 42, 4, 500-510.
10.1016/j.molcel.2011.04.018
2010 Corbett, M. & Gecz, J. (2010). Great expectations: using massively parallel sequencing to solve inherited disorders. Expert Review of Molecular Diagnostics, 10, 7, 833-836.
10.1586/ERM.10.83
2010 Hackett, A., Tarpey, P., Licata, A., Cox, J., Whibley, A., Boyle, J. ... Stratton, M. (2010). CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes. European Journal of Human Genetics, 18, 5, 544-552.
10.1038/ejhg.2009.220
2010 Bahlo, M., Jolly, L., Afawi, Z., Gardner, A., Oliver, K., Tan, S. ... Corbett, M. (2010). A focal Eeilepsy and intellectual disability syndrome is due to a mutation in TBC1D24. American Journal of Human Genetics, 87, 3, 371-375.
10.1016/j.ajhg.2010.08.001
2009 Gecz, J., Shoubridge, C. & Corbett, M. (2009). The genetic landscape of intellectual disability arising from chromosome X. Trends in Genetics, 25, 7, 308-316.
10.1016/j.tig.2009.05.002
2009 Tarpey, P., Smith, R., Pleasance, E., Whibley, A., Edkins, S., Hardy, C. ... Mironenko, T. (2009). A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nature Genetics, 41, 5, 535-543.
10.1038/ng.367
2008 Froyen, G., Corbett, M., Vandewalle, J., Jarvela, I., Lawrence, O., Meldrum, C. ... Scott, R. (2008). Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. American Journal of Human Genetics, 82, 2, 432-443.
10.1016/j.ajhg.2007.11.002
2008 Dibbens, L., Tarpey, P., Hynes, K., Bayly, M., Scheffer, I., Smith, R. ... West, S. (2008). X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nature Genetics, 40, 6, 776-781.
10.1038/ng.149
2007 Field, M., Tarpey, P., Smith, R., Edkins, S., O'Meara, S., Stevens, C. ... Small, A. (2007). Mutations in the BRWD3 gene cause X-linked mental retardation associated with macrocephaly. American Journal of Human Genetics, 81, 2, 367-374.
10.1086/520677
2007 Voss, A., Gamble, R., Collin, C., Shoubridge, C., Corbett, M., Gecz, J. & Thomas, T. (2007). Protein and gene expression analysis of Phf6, the gene mutated in the Borjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity. Gene Expression Patterns, 7, 8, 858-871.
10.1016/j.modgep.2007.06.007
2007 Tarpey, P., Raymond, F., Nguyen, L., Rodriguez, J., Hackett, A., Vandeleur, L. ... Dicks, E. (2007). Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nature Genetics, 39, 9, 1127-1133.
10.1038/ng2100
2006 Sanoudou, D., Corbett, M. A., Han, M., Ghoddusi, M., Nguyen, M. -. A. T., Vlahovich, N. ... Beggs, A. H. (2006). Skeletal muscle repair in a mouse model of nemaline myopathy. Human Molecular Genetics, 15, 17, 2603-2612.
10.1093/hmg/ddl186
2005 Corbett, M. A., Akkari, P. A., Domazetovska, A., Cooper, S. T., North, K. N., Laing, N. G. ... Hardeman, E. C. (2005). An alphaTropomyosin mutation alters dimer preference in nemaline myopathy. Ann Neurol, 57, 42-9.
2001 Corbett, M., Robinson, C., Dunglison, G., Yang, N., Joya, J., Stewart, A. ... Hardeman, E. (2001). A mutation in α-tropomyosinslow affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy. Human Molecular Genetics, 10, 4, 317-328.
10.1093/hmg/10.4.317

Book Chapters

Year Citation
2009 Crawford, J., Partington, M., Corbett, M., Lower, K. & Gecz, J. (2009). Börjeson-Forssman-Lehmann Syndrome. In P. L. Beales, I. S. Farooqi & S. O'Rahilly (Eds.), Genetics of Obesity Syndromes (pp. 187-200). New York: Oxford University Press.
10.1093/med/9780195300161.003.0010

Conference Papers

Year Citation
2011 Berkovic, S., Corbett, M., Schwake, M., Bahlo, M., Dibbens, L., Lin, M. ... Gecz, J. (2011). A NEW FORM OF PROGRESSIVE MYOCLONUS EPILEPSY WITH EARLY ATAXIA AND SCOLIOSIS DUE TO MUTATION IN THE GOLGI PROTEIN GOSR2. 29th International Epilepsy Congress. Rome, ITALY.

Conference Items

Year Citation
2013 Quach, A., Lester, S., Smith, A., Hissaria, P., Al Kindi, M., Heddle, R. ... Costabile, M. (2013). A HAPLOTYPE/DIPLOTYPE ASSOCIATED WITH DELAYED TACI UPREGULATION AND INCREASED RISK OF COMMON VARIABLE IMMUNODEFICIENCY.
2013 Tsai, L., Schwake, M., Corbett, M. A., Gecz, J., Berkovic, S. & Shieh, P. B. (2013). GOSR 2: a novel form of Congenital Muscular Dystrophy. 18th International Congress of the World Muscle Society (WMS). Pacific Grove, California.
10.1016/j.nmd.2013.06.404
2013 Lomax, L. B., Bayly, M., Hjalgrim, H., Moller, R., Vlaar, A. M., Aaberg, K. ... Dibbens, L. (2013). 'North Sea' Progressive Myoclonus Epilepsy: Phenotype of Subjects with GOSR2 Mutation. 65th Annual Meeting of the American-Academy-of-Neurology (AAN). San Diego, CA.
2013 Dibbens, L., de Vries, B., Donatello, S., Heron, S., Hodgson, B., Chintawar, S. ... Cossette, P. (2013). MUTATIONS IN DEPDC5: A MAJOR CAUSE OF FAMILIAL FOCAL EPILEPSY. 30th International Epilepsy Congress. Montreal, CANADA.
  1. 2016. Genetic Pathways to Cerebral Palsy: Alastair MacLennan, Clare van Eyk, Mark Corbett, Morgan Newman, Christopher Barnett. NHMRC. $1,314,158
  2. 2016. Deciphering the non-coding code: Finding the genetic basis for neurological disorders in large, well-studied families. Women’s and Children’s Hospital Foundation, $75,000
  3. 2014. Whole genome sequencing as a diagnostic and research tool to study neurodevelopmental disorders. Channel 7 Children’s Research Foundation, $74,000
  4. 2012. A mutation in LAS1L causes Wilson-Turner Syndrome.Women’s and Children’s Hospital Foundation, $41,500
  5. 2011. Conditional knockout of Phf6, a mouse model for Börjeson Forssman Lehman Syndrome. Women’s and Children’s Hospital Foundation, $17,480
  6. 2011. A study of an intellectual disability and obesity syndrome.  Channel 7 Children’s Research Foundation, $60,000
  7. 2008.  Novel mechanism of mutation by recurrent DNA duplication in patients with intellectual disability; prevalence and biological significance.  WCH foundation project grant.  $50,000.
  8. 2006. Characterisation of PHF6 function and its role in X-linked Mental Retardation.Channel 7 Children’s Relief Fund, Early Career Research Grant. $15,000

Committee Memberships

Date Role Committee Institution Country
2017 - ongoing Member Adelaide Protein Group Adelaide Protein Group Australia
2015 - ongoing Treasurer Adelaide Protein Group Adelaide Protein Group Australia
2012 - 2015 Chair Adelaide Protein Group Adelaide Protein Group Australia
2008 - 2012 Treasurer Adelaide Protein Group Adelaide Protein Group Australia
2006 - ongoing Member Women's and Children's Health Network Animal Ethics Committee Women's and Children's Health Network Australia
Phone
83137938
Campus
North Terrace
Building
Adelaide Health and Medical Sciences Building
Room Number
WS8071.17
Org Unit
Adelaide Medical School

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