Research Biographies

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Medical and Developmental Genetics


Veronica van Heyningen

Contact Details

E-mail address:
Telephone: +44 (0)131 332 2471 (extension 2217)
Fax: +44 (0)131 467 8456
Address: MRC Human Genetics Unit MRC IGMM, University of Edinburgh Western General Hospital, Crewe Road, Edinburgh EH4 2XU
Research Programme: Genes, Environment and Evolution in Eye Development and Malformations: PAX6, SOX2, OTX2



Research Areas

Identifying human disease genes and mutations can reveal how normal biology works and also how it can go wrong in disease. Because many genes and their functions are strongly conserved during evolution, it is possible to use a variety of model organisms including mice, fish and even flies, to study how genes work and interact. Often mutations similar to those that cause disease can be recreated in the model system and studied in great detail, when human patients cannot be studied in the same way. Conversely, there are some non-invasive functional studies in humans that provide information not available from model organisms (eg detailed eye tests, speech and hearing studies, and magnetic resonance imaging). We have identified several genes that lead to overlapping patterns of developmental eye abnormalities, when mutated. Not surprisingly these genes work together in the same pathways. From the different types of mutations, and model organism experiments, we are learning a lot about how developmental regulator genes work and how their expression is fine-tuned. Through hypothesis-driven studies in zebrafish, we are also exploring how environmental factors may interact with mutant genes to alter the outcome of genetic disease

Key/Selected Publications

  • Kleinjan, D.A.; Bancewicz, R.M.; Gautier, P.; Dahm, R.; Schonthaler, H.B.; Damante, G.; Seawright, A.; Hever, A.M.; Yeyati, P.L.; van Heyningen, V. and Coutinho, P. Subfunctionalization of duplicated zebrafish pax6 genes by cis-regulatory divergence.
    PLoS Genet 4(2):e29, 2008 PubMed Abstract

  • Yeyati, P.L.; Bancewicz, R.M.; Maule, J. and van Heyningen, V. Hsp90 selectively modulates phenotype in vertebrate development. PLoS Genet 3(3):e43, 2007 PubMed Abstract

  • Kleinjan, D.A.; Seawright, A.; Mella, S.; Carr, C.B.; Tyas, D.A.; Simpson, T.I.; Mason, J.O.; Price, D.J. and van Heyningen, V. Long-range downstream enhancers are essential for Pax6 expression. Dev Biol 299(2):563-581, 2006 PubMed Abstract

  • Ragge, N.K.; Brown, A.G.; Poloschek, C.M.; Lorenz, B.; Henderson, R.A.; Clarke, M.P.; Russell-Eggitt, I.; Fielder, A.; Gerrelli, D.; Martinez-Barbera, J.P.; Ruddle, P.; Hurst, J.; Collin, J.R.; Salt, A.; Cooper, S.T.; Thompson, P.J.; Sisodiya, S.M.; Williamson, K.A.; Fitzpatrick, D.R.;
    van Heyningen, V. and Hanson, I.M. Heterozygous mutations of OTX2 cause severe ocular malformations. Am J Hum Genet 76(6):1008-1022, 2005 PubMed Abstract

  • Bamiou, D.E.; Musiek, F.E.; Sisodiya, S.M.; Free, S.L.; Davies, R.A.; Moore, A.; van Heyningen, V. and Luxon, L.M. Deficient auditory interhemispheric transfer in patients with PAX6 mutations. Ann Neurol 56(4):503-509, 2004 PubMed Abstract

  • Fantes, J.; Ragge, N.K.; Lynch, S.A.; McGill, N.I.; Collin, J.R.; Howard-Peebles, P.N.; Hayward, C.; Vivian, A.J.; Williamson, K.; van Heyningen, V. and Fitzpatrick, D.R. Mutations in SOX2 cause anophthalmia. Nat Genet 33(4):461-463, 2003 PubMed Abstract

  • Kleinjan, D.A.; Seawright, A.; Schedl, A.; Quinlan, R.A.; Danes, S. and van Heyningen, V. Aniridia-associated translocations, DNase hypersensitivity, sequence comparison and transgenic analysis redefine the functional domain of PAX6. Hum Mol Genet 10(19):2049-2059, 2001
    PubMed Abstract

  • Sisodiya, S.M.; Free, S.L.; Williamson, K.A.; Mitchell, T.N.; Willis, C.; Stevens, J.M.; Kendall, B.E.; Shorvon, S.D.; Hanson, I.M.; Moore, A.T. and van Heyningen, V. PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Nat Genet 28(3):214-216, 2001 PubMed Abstract

  • Engelkamp, D.; Rashbass, P.; Seawright, A. and van Heyningen, V. Role of Pax6 in development of the cerebellar system. Development 126(16):3585-3596, 1999  PubMed Abstract

  • Schedl, A.; Ross, A.; Lee, M.; Engelkamp, D.; Rashbass, P.; van Heyningen, V. and Hastie, N.D. Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities. Cell 86(1):71-82, 1996 PubMed Abstract

  • Fantes, J.; Redeker, B.; Breen, M.; Boyle, S.; Brown, J.; Fletcher, J.; Jones, S.; Bickmore, W.; Fukushima, Y.; Mannens, M.; Danes, S.; van Heyningen, V. and Hanson, I.M. Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. Human Molecular Genetics 4:415-422 1995 PubMed Abstract

  • Hanson, I.M.; Fletcher, J.M.; Jordan, T.; Brown, A.; Taylor, D.; Adams, R.J.; Punnett, H.H. and van Heyningen, V. Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nat Genet 6(2):168-173, 1994 PubMed Abstract

  • Hill, R.E.; Favor, J.; Hogan, B.L.; Ton, C.C.; Saunders, G.F.; Hanson, I.M.; Prosser, J.; Jordan, T.; Hastie, N.D. and van Heyningen, V. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature 354(6354):522-525, 1991 PubMed Abstract

Recent Publications

  • Ravi V, Bhatia S, Gautier P, Loosli F, Tay BH, Tay A, Murdoch E, Coutinho P, van H, V, Brenner S, Venkatesh B, and Kleinjan DA. Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences. PLoS. Genet. 9: e1003177. 2013
    PubMed Abstract
  • Hart AW, Mella S, Mendrychowski J, van H, V, and Kleinjan DA. The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas. 2013
    PubMed Abstract
  • Coutinho P, Pavlou S, Bhatia S, Chalmers KJ, Kleinjan DA, Vanheyningen V: Discovery and assessment of conserved Pax6 target genes and enhancers. Genome Res 21(8): 1349-59,  2011.
    PubMed Abstract
  • Clericuzio C, Hingorani M, Crolla JA, van Heyningen V, Verloes A: Clinical utility gene card for: WAGR syndrome. Eur J Hum Genet 19(4): 2011. PubMed Abstract
  • Ragvin, A.; Moro, E.; Fredman, D.; Navratilova, P.; Drivenes, O.; Engstrom, P.G.; Alonso, M.E.; Mustienes, E.L.; Skarmeta, J.L.; Tavares, M.J.; Casares, F.; Manzanares, M.; van Heyningen, V.; Molven, A.; Njolstad, P.R.; Argenton, F.; Lenhard, B. and Becker, T.S. Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3. Proc.Natl.Acad.Sci.U.S.A 107(2):775-780, 2010 PubMed Abstract
  • Asai-Coakwell, M.; French, C.R.; Ye, M.; Garcha, K.; Bigot, K.; Perera, A.G.; Staehling-Hampton, K.; Mema, S.C.; Chanda, B.; Mushegian, A.; Bamforth, S.; Doschak, M.R.; Li, G.; Dobbs, M.B.; Giampietro, P.F.; Brooks, B.P.; Vijayalakshmi, P.; Sauve, Y.; Abitbol, M.; Sundaresan, P.; van Heyningen, V.; Pourquie, O.; Underhill, T.M.; Waskiewicz, A.J., and Lehmann, O.J. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Hum Mol Genet 18(6):1110-21, 2009 PubMed Abstract


van Heyningen, V. and Hill, R. E.(Eds.). Long-Range Control of Gene Expression, Advances in Genetics Vol 61, 2008