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Génétique de la Sclérose En Plaques: Héritabilité manquante et Charge génétique

Abstract : Multiple Sclerosis (MS) is a multifactorial disease, resulting from an interaction between genetics and unknown environmental factors. During the last years, the identification of several predisposing genetic polymorphisms constituted a real breakthrough in the understanding of MS genetic architecture. In 2011, a large international study identified 57 non-MHC genomic regions associated with MS susceptibility. However, the genetic part of the disease explained by these factors was evaluated to only be 17% of total MS heritability. During my PhD, I leaded or participated to several projects aiming to identify the so-called " missing heritability ", based on different strategies: to increase the sample sizes in order to amplify the statistical power of the studies, to identify the causative variants within previously highlighted genomic regions, to study un-investigated genomic regions and genetic interactions between variants of a same biological pathway, to study the individual genetic burden. One of the projects extended the number of MS non-MHC-variants to 110, increasing the known part of heritability from 17% to 23%. In order to go further in MS genetics, other hypotheses should be explored, as (a) the identification of variants specific to one sub-population (French, English ...), (b) the identification of new risk variants localized in previously highlighted regions in populations of non-carriers of known risk alleles of these regions, (c) the study of the Copy-Number Variations. Finally, the major challenge of next years will be to correlate genetic risk variants to functional effects and to comprehensive MS Phenome.
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https://tel.archives-ouvertes.fr/tel-00929806
Contributor : Vincent Damotte <>
Submitted on : Monday, January 13, 2014 - 11:26:08 PM
Last modification on : Friday, May 29, 2020 - 4:00:23 PM
Document(s) archivé(s) le : Monday, April 14, 2014 - 12:10:13 AM

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  • HAL Id : tel-00929806, version 1

Citation

Vincent Damotte. Génétique de la Sclérose En Plaques: Héritabilité manquante et Charge génétique. Génétique humaine. Université Pierre et Marie Curie - Paris VI, 2013. Français. ⟨tel-00929806⟩

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