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  Director : Cécile Julier (cjulier@pasteur.fr)



The main aim of our studies is the mapping, identification and study of genes involved in the susceptibility/resistance to multifactorial diseases: one autoimmune disease, type 1 diabetes (T1D), and infectious diseases, malaria and dengue. The genetic approach, common to these two types of diseases, is based on familial studies as well as population-based studies (case/control). For T1D, two susceptibility genes are already known, HLA and insulin, and our research is focusing on the identification of the other genes, whose chromosomal localisation we have been able to confirm in some cases.



Genetic susceptibility to type 1 diabetes in human Responsible: Cécile Julier

Based on our previous studies performed in French, North-American and Scandinavian families with at least two siblings affected with T1D, we were able to confirm linkage of T1D to 11q13 (IDDM4 locus) and 6q21 (IDD15 locus) regions, with stringent statistical criteria. These regions, and new ones that we identified in our recent genome-wide scan in Scandinavian families, are the focus of detailed genetic studies in our laboratory, in order to identify the responsible genes and variants. These studies are mostly based on systematic association screening in these regions, with complementary approaches: (1) studies of consanguineous T1D families and monogenic or oligogenic subtypes, (2) association studies in sub-groups defined according to phenotypic and genetic criteria. In addition, we participate in an international consortium on T1D (T1DGC), whose aim is to organize genetic studies of T1D on a large scale.

Wolcott-Rallison syndrome and EIF2AK3 gene Responsible: Cécile Julier

Wolcott-Rallison syndrome is a very rare autosomal recessive disorder, characterized by the association of a neonatal permanent insulin-dependent diabetes and epiphyseal dysplasia. From the study of two consanguineous families, with a total of 10 individuals, 5 of which were affected children, and 1 was a healthy child, we were able to identify the gene mutated in this disorder. This is EIF2AK3 (translation initiation factor 2-a kinase 3), in which we identified mutations segregating with the disorder in the two families studied. This gene represents a potential candidate for frequent forms of diabetes (type 1 and type 2). Interestingly, the region of this gene (2p12) shows linkage to T1D in Scandinavian families (see above), which strengthens our hypothesis that this gene may be involved in the susceptibility to T1D.

Genetic studies of susceptibility to infectious diseases: malaria and dengue Responsible: Anavaj Sakuntabhai, Cécile Julier

Several genes have been implicated in the resistance to severe malaria. Our project is to identify genes involved in the variability of phenotypes related to malaria infection, and to study the mechanisms involved. These studies are based on the analysis of families located in areas of endemic malaria: Senegal and Thailand. Many epidemiological, clinical and immunological studies have been performed in the Senegalese families during the last 10 years (Pasteur Institutes of Paris and Dakar, IRD). In these families, we found evidence for the implication of genetic factors in several relevant phenotypes. We performed a genome-wide scan in these families (collaboration with the Centre National de Génotypage, Evry) with complementary studies of candidate genes and regions, in order to map and identify these genetic factors. A similar study is in progress in Thai families.

Dengue virus is endemic in several tropical countries, particularly in South-East Asia, where the infection results in 1-2% of cases in severe forms, hemorrhagic or shock, which can lead to death. Our project is to identify susceptibility genes for these severe cases, using a "candidate genes" approach in case/control populations for severe forms of dengue, which have been collected in Thailand.

Keywords: autoimmune diseases, infectious diseases, type 1 diabetes, malaria, dengue, genetic susceptibility, human genetics


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  Office staff Researchers Scientific trainees Other personnel
  Julier, Cécile, INSERM (DR2, cjulier@pasteur.fr)

Sakuntabhai, Anavaj, Institut Pasteur, (chargé de recherche, anavaj@pasteur.fr)

Chayanon Peerapittayamongkol, post-doc, poste vert INSERM

Senée, Valérie, post-doc, grant from FRM

Ndiaye, Rokhaya, thesis student

Ghandil, Pegah, thesis student

Duchatelet, Sabine, thesis student

Kalayanarooj, Sita, thesis student (Thaïlande)

Samadi, Zarah, Institut Pasteur of Iran, grant from the Pasteur Institutes’ network

Kirchner, Johanne, DEA student

Casadémont, Isabelle, (Ingénieur de Recherche, Institut Pasteur, igautier@pasteur.fr)

Joffret, Marie-Line, (Ingénieur de Recherche, Institut Pasteur, mjoffret@pasteur.fr)

Blanc, Hervé, (Technicien Supérieur, Institut Pasteur, herveb@pasteur.fr)

Roux, Cécile, (Secrétaire, Institut Pasteur, croux@pasteur.fr)

Activity Reports 2002 - Institut Pasteur

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