Inserm UMR-S-958 “Genetics of diabetes”
University Paris Diderot - Paris 7
School of Medicine
10 avenue de Verdun
75010 Paris, France
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. It involves both "wet lab" and bioinformatics to analyze high-throughput data using eQTL mapping strategies.
Keywords: immunogenetics, MHC, autoimmunity, type 1 diabetes, eQTL mapping, multifactorial genetics, biostatistics
My current project aims at identifying new MHC genes involved in the susceptibility to type 1 diabetes using a genetical genomics approach that combines genetic studies and high-throughput functional genomics approaches. More specifically, I use transcriptomic data and eQTL mapping to identify MHC genes differentially expressed on haplotypes having opposing effects on the disease risk.
This research is supported by the Juvenile Diabetes Research Foundation, the NIH and the PHC-Alliance.
I obtained a Ph.D in genetics from the University Paris Descartes in France in 2004. I was working in the laboratory of Dr Henri-Jean Garchon, where I analyzed the multifaceted role of the MHC in the genetic predisposition to acquired autoimmune myasthenia gravis and in the regulation of autoantibody expression (Vandiedonck et al. 2004, PNAS; Vandiedonck et al. 2005, J Autoimmunity). I also reported the first association of the gene PTPN22 with the disease (Vandiedonk et al., 2006, Ann Neurol) and I identified an association of HLA-A with the disease form associated with a thymoma (Vandiedonck et al. 2009, J Neuroimmunol). Finally, I participated in the study of the gene encoding the target autoantigene CHRNA1 that revealed a new mechanism of central tolerance breakdown involving IRF8 and AIRE (Giraud et al. 2007, Nature).
In the MHC region, the final identification of the causal variants has been rendered difficult by the linkage disequilibrium that 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, I joined in 2005 the laboratory of Dr Julian Knight (http://www.well.ox.ac.uk/knight-j) (Wellcome Trust Centre for Human Genetics, Oxford University) as a postdoctoral scientist. There, using a custom array accounting for MHC polymorphism, I generated the first strand-specific haplo-spliceo-transcriptome map of the MHC (access the map here). This study revealed abundant haplotypic differences in gene expression and that alternative splicing is more frequent in the MHC than genome-wide (Vandiedonck et al., 2011, Genome Research).
I 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 (Taylor et al, 2008, NAR) and was involved in the development of strategies to investigate allele-specific expression (Campino et al, 2008, PLoS One; Holt et al., 2011, J Allergy Clin Immunol).
In July 2009, I came back to France where I joined the research laboratory Inserm UMR-S-958 "Genetics of diabetes" of Dr Cécile Julier. After a senior postdoc position, I obtained a permanent position as Associate Professor of Biostatistics. During my research time, I conduct a project applying the genetical genomics approach to type 1 diabetes.
The team in June 2012 (from left to right: Neda Rezaei, Claire Vandiedonck, Windy Luscap, Azadeh Saffarian)
Vandiedonck C, Taylor MS, Lockstone HE, Plant K, Taylor JM, Durrant C, Broxholme J, Fairfax BP and Knight JC (2011) Pervasive haplotypic variation in the spliceo-transcriptome of the human MHC. Genome Research, 2011 Jul ; 21(7) :1042-54 [PMID:21628452].
Cover artpainted by Françoise Vandiedonck
(click here for a more resolutive picture):
Comment in :
Muers M (2011) Complex disease: ups and downs at the MHC.
Nature review genetics, 2011 Jun 17 ; 12(7) :456-7 [PMID:21681207].
Vandiedonck C and Knight JC (2009). The human Major Histocompatibility Complex as a paradigm in genomics research. Brief Funct Genomics, 2009 Sep;8(5):379-94 [PMID:19468039].
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, 2009 May 29;210(1-2):120-3 [PMID:19278738]
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, 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, 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]
My current h-index is: 8
For a complete list of my publications, follow the PubMed link.