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Post-doctoral Research Scientist

claire-photo.jpegMapping haplotype-specific transcription in the classical MHC

My main research interest is the genetics of autoimmune diseases, focusing on their prime genetic factor, the human Major Histocompatibility Complex (MHC). My work is situated at the interface of mutifactorial genetics, genomics, and transcriptomics, and involves both "wet lab" and bioinformatics.

Prior to working in Oxford, I obtained a Ph. D in genetics from the University Descartes-Paris  in 2004. I was working in the laboratory of Dr Henri-Jean Garchon, where I analysed the multifaceted role of the MHC in the genetic predisposition to acquired autoimmune myasthenia gravis and in the regulation of autoantibody expression.

However, the final identification of the causal variants has been rendered difficult by the linkage disequilibrium, especially in the MHC where it extends over long distances. Analysis of modification of MHC gene expression appears then as a necessary complement to help identify the disease variants.

With this perspective in mind, in 2005 I joined the laboratory of Dr Julian Knight in Oxford. My main project aims at identifying polymorphisms that modulate MHC gene expression, in particular polymorphisms found on common haplotypes associated with susceptibility to autoimmune disease. I have defined sites of haplotype-specific transcription occurring across the classical MHC which we are complimenting by mapping sites of DNase hypersensitivity with Dr Maxim Freidin.

mhchistory.jpegI have also had a special interest in studying the expression of two emblematic genes of the MHC central class III region, the TNF and LTA. I am finally involved in the development of strategies to investigate allele-specific expression, in collaboration with Dr Susana Campino (Sanger Centre, UK).

Prior to my D.Phil, while graduating as an M.Sc at University Pierre et Marie Curie, I had acquired lab experience in genetics in three laboratories : I worked in 1998 on lipoatrophic diabetes with Dr Jocelyne Magré in the lab of Pr Capeau in Paris; on insulin resistance syndrome and type 2 diabetes in the laboratory of Dr Froguel at the Pasteur Institute in Lille in 1998 and on progressive pseudo-rheumatoid dysplasia under the supervision of Dr. Judith Fischer at Genethon in 1997.

Email: vandiedo@well.ox.ac.uk

Keywords: Immunogenetics, MHC, Autoimmunity, Myasthenia gravis, Type 1 Diabetes, Genetics, eQTL mapping, Regulatory variants, Genetical genomics, Alternative splicing

Publications

  • Vandiedonck C and Knight JC (2009). The human Major Histocompatibility Complex as a paradigm in genomics research. Brief Funct Genomic Proteomic. In Press.
  • Vandiedonck C, Raffoux C, Eymard B, Tranchant C, Dulmet E, Krumeich S, Gajdos P, Garchon HJ (2009) Association of HLA-A in autoimmune myasthenia gravis with thymoma. J Neuroimmunol. In Press. [PMID: 19278738]
  • Campino S, Forton J , Raj S, Mohr A , Auburn S , Fry A, Mangano V, Vandiedonck C, Richardson A, Rockett K, Clark T, Kwiatkowski D (2008) Validating discovered cis-acting regulatory genetic variants: application of an allele specific expression approach to HapMap populations. Plos One, 3(12):e4105. Epub 2008 Dec 31. [PMID: 19116668] [link to http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004105]
  • Taylor JM, Wicks K, Vandiedonck C, Knight JC (2008) Chromatin profiling across the human tumour necrosis factor gene locus reveals a complex, cell type-specific landscape with novel regulatory elements. Nucleic Acids Res, 36(15):4845-62. [PMID: 18653526]
  • Giraud M, Vandiedonck C, Garchon HJ (2008) Genetic factors in autoimmune myasthenia gravis. Annals of New York Academy of Sciences, 1132:180-92. [PMID: 18567868]
  • Giraud M, Taubert R, Vandiedonck C, Ke X, Levi-Strauss M, Pagani F, Baralle FE, Eymard B, Tranchant C, Gajdos P, Vincent A, Willcox N, Beeson D, Kyewski B, Garchon HJ (2007) An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature, 448:934-937. [PMID: 17687331]
  • Vandiedonck C, Capdevielle C, Giraud M, Krumeich S, Jais JP, Eymard B, Tranchant C, Gajdos P, Garchon HJ (2006) Association of the PTPN22*R620W Polymorphism with Autoimmune Myasthenia Gravis. Annals of Neurology, 59:404-407. [PMID: 16437561]
  • Vandiedonck C, Giraud M, Garchon HJ (2005) Genetics of autoimmune myasthenia gravis: the multifacted contribution of the HLA complex. J Autoimmunity, vol 25, Supp1:6-11. [PMID: 16260117]
  • Vandiedonck C, Beaurain G, Giraud M, Hue-Beauvais C, Eymard B, Tranchant C, Gajdos P, Dausset J, Garchon HJ (2004) Pleiotropic effects of the 8.1 HLA haplotype in patients with autoimmune myasthenia gravis and thymus hyperplasia. Proc Natl Acad Sci U S A, 101:15464-15469. [PMID: 15489265]
  • Fischer J, Urtizberea JA, Pavek S, Vandiedonck C, Bruls T, Saker S, Alkatip Y, Prud'homme JF, Weissenbach J (1998) Genetic linkage of progressive pseudorheumatoid dysplasia to a 3-cM interval of chromosome 6q22. Hum Genet 103:60-64. [PMID: 9737778]

Sponsored by: Five years postdoctoral position at the Wellcome Trust Centre for Human Genetics, Oxford University (05/2005 till date), Doctoral fellowship from the French Association pour la Recherche sur le Cancer (ARC) (10/2004 to 12/2004),  One-year doctoral fellowship from the French Association Against Myopathies (AFM) (10/2003 to 09/2004),  Three-years Ph.D. grant, from the French Ministry of Higher Education, Research and Technology (10/2000 to 09/2003)